15: Cell Signaling and Communication

Introduction

· Survival of an organism depends on appropriate responses to the environment, both internal and external.

· Just as it is important for humans to respond appropriately in their daily lives, cells must respond appropriately to stay alive.

· Cells are like tiny computers processing literally millions of inputs and generating millions of outputs daily.

· Signals originate from the general environment or from other cells, local or distant.

· Three sequential processes are involved in the cell’s response to a signal:

· The signal binds to a receptor protein

· The binding cause a message to be sent to the cell’s cytoplasm and amplified.

· The cell changes its activity in response to the signal.

Signals

· Both prokaryotic and eukaryotic cells must process information from their environment and calculate appropriate responses.

· Signals might be chemical molecules or physical stimuli like light or heat.

· Cells must be set up to interpret signals—not all cells can interpret all signals.

· To interpret a signal, a cell must have the appropriate receptor protein.

· In multicellular organisms, all cells have the genetic information for all receptor proteins, but due to differential gene expression, different cells have different receptors.

· Cells have specific receptor proteins that interact with specific signals.

· Signal transduction is the conversion of a signal from one form to another.

Cells receive signals from the physical environment and from other cells

· Multicellular organisms' internal cells are exposed to extracellular fluids and other cells, from which they receive information.

· A few of the many types of signals in animal cells are hormones, neurotransmitters, chemical messages from the immune system, CO₂, and H⁺.

· O₂ and changes in osmotic pressure are also signals.

· In large animals, signals reach targets via diffusion as autocrine or paracrine signals when the target is close.

· When the target is distant, signals travel by circulation in the blood. (See Figure 15.1.)

· Autocrine signals, for example, are signals generated by the same cells upon which they act.

· Paracrine signals diffuse to and affect nearby cells.

· Signals and their interpretation create the order we call life.

· Signals are used every moment of life from the period of earliest embryonic development.

· Signals and their interpretation provide information to the cells of multicellular organisms on their location within a tissue, organ, and organism.

· Signals are needed for wound healing.

· They are also needed for cell replacement and programmed cell death (apoptosis).

· Moment by moment signals provide information essential for the maintenance of appropriate concentrations of nutrients.

· Signals and their processing provide information from light and sound.

· Signals are involved in a multitude of other cellular and manifestly organismal activities.

· Signals are involved in directing which genes a cell will express.

· The process from signal detection to final response is a signal transduction pathway.

Signaling involves a receptor, transduction, and effects

· Cells must be able to detect the availability of nutrients.

· Cells must maintain homeostasis.

· When scientists discuss cell signaling, they tend to describe it as a series of events that occur.

· Generally, many of the events described in the pathway are actually happening at the same time.

· For example, some signals will just be arriving at the cell when the effects of previous signals are still being processed.

· Just as it can be explained how, when you are talking to someone on the phone who might be in another country, your voice is first converted to electrical impulses, then digital information, then electrical impulses, and then back into sound, we can describe what happens to cell signals as they are received, interpreted by cells, and transformed into appropriate outcomes.

· The way in which single-celled organisms respond to signals has much in common with signaling in more complex animals and plants.

· A sample prokaryotic signal pathway is shown in Figure 15.3.

· In E. coli, EnvZ is a transmembrane protein.

· It is found in the bacterium's plasma membrane.

· The bacteria, E. coli, have two membranes, a plasma membrane, which is innermost, and an outer membrane.

· Part of the EnvZ protein faces the space between the two membranes. (Part is transmembrane; part faces the inside of the cell.)

· Increases in the ion concentration in the space between the two membranes causes the EnvZ protein to change shape.

· The shape change, initiated in the intermembrane space, affects regions on both sides of the membrane.

· The EnvZ becomes an active enzyme, a protein kinase, due to the shape change. The enzyme activity is found on the region of EnvZ facing the cytoplasm.

· Protein kinases are common intermediaries in signal transduction. They add a phosphate to a certain amino acid of the proteins for which they are specific.

· The EnvZ protein first catalyzes phosphorylation of one of its own histidine residues.

· This again causes a conformational change.

· Now, OmpR, another protein, can bind to EnvZ.

· The EnvZ transfers its phosphate to OmpR.

· The OmpR, in a sense, dephosphorylates the EnvZ, resetting EnvZ back to its original state. Restoration of initial states is an important characteristic of signal transduction pathways.

· The OmpR, which is a DNA-binding protein, binds the E. coli’s DNA, initiating transcription of the ompF gene.

· The protein made by the ompF gene, the OmpF protein, inserts into the outer membrane, preventing solutes from entry, and restoring the appropriate osmotic condition.

· The steps in this signal transduction pathway occur in many other signal transduction systems in animals and plants:

· A receptor changes conformation (shape) upon binding its specific signal molecule.

· Conformational change exposes a protein kinase.

· Phosphorylation alters the functioning of a protein.

· The signal is amplified.

· Transcription factors are activated.

· Altered synthesis of specific proteins occurs.

· Protein action alters cell activity.

Receptors

· A cell responds to only a few of the signals it receives.

· Which cell makes which receptor is genetically determined.

Receptors have specific binding sites for their signals

· A ligand is the signaling molecule that binds the receptor. (See Figure 15.4.)

· Receptors change shape when bound.

· Ligands are often only signaling molecules, not metabolites (unlike enzyme–substrate interactions).

· Receptors bind ligands according to chemistry’s law of mass action (see Chapter 2).

· Therefore, binding is reversible although favoring binding moves the equilibrium point far to the right.

· The concentration necessary to saturate receptors depends on the affinity of the receptor for the ligand.

· Some have high affinity, which means low concentration can have large effects.

· Some receptors bind inhibitors as well as signals.

· Inhibitors that bind the receptor’s ligand-binding site are called competitive inhibitors.

· Inhibitors that bind at sites other than the ligand-binding site are called noncompetitive inhibitors.

There are several types of receptors

· The cellular location of receptors depends on the nature of their ligands.

· There are several major classes of signaling molecules depending on polarity.

· Nonpolar signaling molecules can pass through the plasma membrane. (See Figure 15.5.)

· Steroids are examples of nonpolar signaling molecules.

· Estrogen, for example, can easily diffuse across the plasma membrane.

· Steroids bind receptors that are located in the cytoplasm.

· Only cells expressing the genes that code for a receptor of a certain steroid can be affected by that steroid.

· There are also other signal molecules besides steroids that can pass directly through the membrane.

· Large or polar signals cannot cross the membrane.

· They must interact with the outside portion of receptors embedded in the cell's membrane.

· Receptors for large or polar signals are generally transmembrane proteins.

· Insulin is a protein hormone that interacts with a transmembrane receptor. (See Figure 15.5.)

· Three well-studied types of transmembrane receptors in complex eukaryotes are ion channels, protein kinases, and G protein-linked receptors.

· Ion channels:

· Some ion channel proteins, acting as “gates,” are signal receptors.

· Channel proteins can open to let in or out, or close to restrict, certain ions. (See Figure 15.6.)

· The signal to open or close the channel can be chemical, light, sound, pressure, or voltage.

· An example of a gated ion channel is the acetylcholine receptor. (See Figure 15.6.)

· Protein kinase receptors:

· Protein kinase involvement in cell signaling is diverse and common.

· Some eukaryotic receptor proteins become kinases when activated.

· A phosphate is transferred from ATP to a certain amino acid (residue) in a protein, changing the state of the protein from active to inactive, or vice versa.

· Sometimes the protein kinase phosphorylates itself. This is called autophosphorylation.

· In eukaryotic cells, the usual target for phosphorylation is tyrosine, serine, or threonine (the terminal end of these amino acids’ R group).

· Insulin receptors are examples of protein kinase receptors. (See Figure 15.7.)

· The insulin receptor consists of two a subunits, which bind the ligand (insulin) outside the cell, and two b subunits, which transmit the signal to the cytoplasm.

· Two molecules of insulin (one for each a subunit) must bind to the receptor in order to transmit the signal.

· After binding insulin on its extracellular surface, the receptor changes its shape.

· The shape change exposes a protein kinase active site at the cytoplasmic region of the receptor.

· Like the EnvZ receptor in E. coli, the insulin receptor self-phosphorylates.

· The insulin receptors can then target and phosphorylate other cytoplasmic proteins called insulin response substrates.

· These proteins then initiate other cellular activities including the insertion of glucose transporters into the cell membrane.

· Insulin and its receptors are part of the family of enzyme-linked transmembrane receptor systems.

· G protein-linked receptors:

· Another type of signal receptor, the “seven-spanning G protein-linked receptor,” is at the beginning of a modular-type system of information transfer. (See Figure 15.8.)

· This system consists of at least three units: a receptor that spans the plasma membrane, a G protein, and an effector protein.

· What defines a G protein?

· G proteins have a binding site for the G protein-linked receptor and for a nucleotide called GDP/GTP.

· GTP and GDP are like ATP and ADP; they are ribonucleotides. Whereas ATP is a common energy molecule and also a building block for RNA, GTP is used in some signaling pathways and also as a building block for RNA.

· G proteins have GTPase activity as well. This means G proteins can hydrolyze the terminal phosphate from GTP to form GDP.

· G proteins are active when they are bound to GTP and inactive when they are bound to GDP.

· G proteins are also important constituents of the cell’s cytoskeleton.

· As with many other receptor systems, a signal from outside the cell binds the G protein-linked receptor and changes its shape both outside and inside the cell.

· The changed shape in the internal domain of the receptor causes it to bind a membrane-associated G protein.

· When the receptor and the G protein bind, a subunit of the G protein releases its GDP and acquires a GTP.

· The GTP activates the subunit of the G protein, which separates from the rest of the G protein.

· The GTP-bearing subunit moves along the plane of the internal plasma membrane until it encounters and activates an effector molecule.

· After the interaction, the G protein hydrolyzes its GTP, thereby switching its own activity back to the initial off state.

· To complete the cycle, this G protein subunit must find another G protein receptor, minus the subunit, and associate with it.

· When a signal causes the subunit to release its GDP, the cycle begins again.

· G proteins can either activate or inhibit effectors. Epinephrine (the “fight or flight” hormone) illustrates both possibilities.

· In the heart, a G protein-linked receptor system activates an enzyme.

· The heart is set up to respond to epinephrine as a signal.

· G protein-linked receptors in heart muscles bind epinephrine.

· The associated G protein gets activated in response to the change in receptor shape.

· The G protein subunit swaps GDP for GTP and diffuses along the plasma membrane.

· It activates another enzyme found associated with the cytosolic face, which makes a small molecule called cAMP (cyclic adenosine monophosphate).

· cAMP, in turn, has a wide range of effects on the cell, including glucose mobilization and muscle contraction.

· In the smooth muscle cells surrounding blood vessels lining the digestive tract, a G protein-linked receptor system inhibits an enzyme.

· The system begins the same way as in the heart: Epinephrine activates the receptor, which binds a G protein, which activates a subunit, which diffuses along the inside of the plasma membrane.

· In this case, however, when the G protein subunit encounters its target enzyme, it inhibits the enzyme instead of activating it. As a result, the muscles relax, the blood vessel dilates (its diameter increases), and the flow of nutrients away from the stomach to the rest of the body increases.

· This example demonstrates that the same signal and initial signaling mechanism can have different consequences in different cells.

· The response depends on how the cell is set up to respond.

· Cytoplasmic receptors:

· Not all signal receptors act at the plasma membrane.

· Some signaling molecules get through the plasma membrane and into the cytoplasm, where they react with receptor proteins. (See Figure 15.9.)

· Steroid hormones are an example.

· Steroids enter all cells of the body.

· Some cells have cytoplasmic receptors for certain steroids such as cortisol.

· The intracellular receptor binds to the steroid, changing the shape of the receptor.

· This causes it or some event-related component to bind DNA and influence gene expression as a transcription factor.

Transducers

· Signaling is a process of transducing.

· An example of transducing is the conversion of electrical impulses to sound in common loudspeakers.

· Transducers convert signals from one form to another.

· Direct transduction results from the action of the receptor itself on effector proteins. Direct transduction occurs at the plasma membrane. (See Figure 15.10a.)

· Indirect transduction, which is more common, uses a second messenger to mediate the interaction between receptor binding and cellular reaction. (See Figure 15.10b.)

· These can cause signals to branch, converge, or amplify.

· Neither direct nor indirect transduction is a single event. In both cases, the signal initiates a series of interactions of protein-to-protein events that eventually lead to a final response.

Protein kinase cascades amplify a response to receptor binding

· "Cascade" is defined as a series of steep waterfalls, or as a connected series, as of amplifiers, for increasing an output.

· A protein kinase cascade is direct signal transduction that catalyzes the phosphorylation of target proteins.

· Details of a certain protein kinase cascade were discovered from the investigation of Ras protein inhibition as treatment for bladder cancer. (See Figure 15.11.)

· Ras protein activates a protein kinase and is a G protein.

· It is a G protein because exchanging GDP for GTP switches on the protein kinase activity, and normally it has GTPase activity.

· The Ras protein in these cancer cells is always bound with GTP because the GTPase activity is inoperative.

· Therefore, the Ras protein causes constant phosphorylation.

· The result is continuous cell division (cancer).

· Ras is part of a protein kinase cascade that influences cell division.

· The pathway is called a kinase cascade because each kinase in the pathway phosphorylates the next.

· Ras in normal cells is usually activated by a transmembrane receptor protein.

· Protein kinase receptors stimulate the protein kinase cascade right at the plasma membrane.

· At first glance, a protein kinase cascade might seem unnecessarily complicated, but there are at least three advantages to having many kinase steps in signal transduction:

· Each activated protein kinase can phosphorylate many target proteins, so amplification of the signal occurs at each step, and a small input signal becomes a large output signal.

· Information from a signal at the cell membrane is transferred to the nucleus.

· Having a variety of steps affecting different target proteins allows for a variety of responses by different cells to the same signal.

Cyclic AMP is a common second messenger

· Indirect transduction and consequent stimulation of cell events is more common than direct transduction.

· Scientists investigating the effects of epinephrine on liver cells discovered cyclic AMP (cAMP) as a second messenger.

· Studying the sequence of events by breaking apart liver cells, they learned that to activate an enzyme called phosphorylase, both plasma membrane and signal hormone (epinephrine) were necessary.

· They incubated broken plasma membranes with epinephrine, then removed the plasma membranes and added the resulting solution to liver cell cytoplasm that contained inactivated phosphorylase enzyme.

· The phosphorylase enzyme became activated.

· Therefore, the epinephrine and plasma membrane must have generated a soluble second messenger.

· This was found to be cAMP. (See Figure 15.12.)

· The cAMP molecule is a small cyclic nucleotide generated from ATP.

· The enzyme adenylyl cyclase produces cAMP using ATP as a substrate. Adenylyl cyclase is activated to produce cAMP by an activated G protein subunit.

· cAMP controls many different cellular activities by amplifying signals which then activate many enzyme targets.

· Like other second messengers, cAMP is not an enzyme. Second messengers act as cofactors or allosteric regulators of target proteins.

· cAMP has two major kinds of targets: ion channels and protein kinases.

· Some cells are set up to respond to cAMP uniquely.

· Certain cell types, like the follicular cells of the ovary, have unique receptors, which when bound by their ligand cause a rise in cytosolic cAMP.

· Downstream, this influences steroid synthesis.

Two second messengers are derived from lipids

· Phospholipids are the predominant molecules in cell membranes.

· Certain phospholipids get hydrolyzed by an enzyme called phospholipase C. (See Figure 15.13.)

· The two parts generated by the hydrolysis—IP₃ and DAG—each become second messengers.

· What activates the phospholipase C?

· A signal at the outside of the cell attaches to the ligand-binding site of the receptor protein.

· This is a G protein-associated receptor protein.

· The G protein subunit swaps GDP for GTP and becomes active.

· This particular G protein subunit is specific for phospholipase C.

· It slides around the internal face of the plasma membrane until it encounters a phospholipase C molecule.

· Active phospholipase C hydrolyses the phospholipid called phosphatidyl inositol into inositol triphosphate (IP₃) and diacylglycerol (the two fatty acid tails of the lipid, abbreviated DAG).

· These second messengers trigger many cellular events.

· One of DAG’s targets is a membrane-bound enzyme, a kinase, called protein kinase C (PKC).

· IP₃ diffuses throughout the cytoplasm until it contacts certain Ca²⁺ channels found in the endoplasmic reticulum (ER).

· Calcium levels are normally low in the cytosol and high in the ER.

· When IP₃ opens the Ca²⁺ channels in the ER, Ca²⁺ diffuses down the concentration gradient into the cytoplasm.

· The Ca²⁺ ion can also stimulate its own release from intracellular stores.

· So far we have seen that one signaling event outside the cell diverges into two with the generation of two different second messenger molecules.

· These two signaling paths converge at protein kinase C.

· To be activated, protein kinase C needs both DAG and Ca²⁺; the Ca²⁺ is provided when IP₃ opens the Ca²⁺ channels in the ER.

· A number of other events that are not convergent also occur.

Calcium ions are involved in many transduction pathways

· Calcium ions are also second messengers.

· Ca²⁺ concentration in the cytoplasm is usually only about 0.1 mM.

· The concentration is kept low via active transport, both out of the cell and into the ER.

· Unlike cAMP, Ca²⁺ cannot be manufactured in the cell; it must be imported.

· Many different signals cause Ca²⁺ channels to open, including IP₃.

· The entry of a sperm into an egg cell also causes Ca²⁺ channels to open. (See Figure 15.14; this figure is available among the photographs on the Instructor’s Resource CD-ROM.)

· Another signal that opens Ca²⁺ channels is electrical depolarization in muscle cells.

· Once a signal triggers Ca²⁺ channels to open, Ca²⁺ concentration rapidly rises to approximately 100 times the resting concentration.

· The calcium ions then affect the activities of cellular proteins.

· One example is protein kinase C as discussed before.

· Ca²⁺ also binds to Ca²⁺ channel proteins, triggering additional releases of Ca²⁺.

· This can be described as a positive feedback loop.

· Calcium ions bind to a calcium-binding protein called calmodulin.

· The calmodulin can activate certain proteins.

· Calmodulin has four calcium binding sites for Ca²⁺.

· At low Ca²⁺ concentrations, the chance that all four Ca²⁺ binding sites are occupied at once is low.

· At high Ca²⁺ concentrations, the probability is sufficient and some of the calmodulin molecules become active via a change in conformation.

· Calmodulin then can activate target molecules.

· One target in muscle cells is a myosin-specific protein kinase needed for initiating muscle contraction.

Nitric oxide is a gas that can act as a second messenger

· Nitric oxide (NO) is a gas (common in air pollution) that was found to be a second messenger by scientists studying the effects of acetylcholine.

· Acetylcholine causes the relaxation of smooth muscles of the blood vessels. (See Figure 15.15.)

· The sequence of events understood then was as follows:

· Acetylcholine molecules bind G protein-linked receptors.

· The activated G protein subunits trigger phospholipase C to hydrolyze lipid.

· The previously discussed series of events would follow with the uniqueness being a downstream target, and the involvement of a cyclic nucleotide similar to cAMP called cGMP.

· The downstream target was a tissue-specific protein kinase, which via phosphorylation causes muscle relaxation.

· This was determined from blood vessels in intact animals.

· Isolated strips of arterial tissue failed to respond, however.

· After difficult work, it was discovered that NO was needed.

· NO was produced by a layer of endothelial cells closely associated with the smooth muscle cells.

· Acetylcholine caused increased Ca²⁺ levels in these epithelial cells.

· In these cells, the elevated Ca²⁺ levels caused, among other things, the activation of NO synthase, the enzyme that makes NO, a very unstable molecule.

· NO diffuses rapidly from the epithelial cells to the nearby smooth muscle cells.

· In the smooth muscle cells of blood vessels, NO stimulates the formation of cGMP.

· The discovery of NO as a second messenger provided the beginnings of an understanding of the mechanism of how nitroglycerin actually works.

· Nitroglycerin has been used for more than a century to treat angina.

· Nitroglycerin releases NO, which results in relaxation of the blood vessels and increases blood flow to the heart.

· Even today, some drugs are used to treat patients because they work, but no one knows how or why they are effective.

Signal transduction is highly regulated

· Often, cells must return to previous states and need to regulate the signal transduction mechanism.

· Responsiveness of cells to stimuli depends on returning quickly to a restored state.

· NO molecules, for example, break down quickly, being unstable.

· Regulation of the NO concentration is dependent on how much is made.

· Ca²⁺ concentrations are restored to normal by mechanisms such as membrane pumps and ion channels that close the Ca²⁺ channels and pump Ca²⁺ out of the cytosol.

· Protein kinase cascades are interrupted by protein phosphatases that remove the added phosphates, deactivating the kinases.

· GTPases deactivate G proteins by converting GTP to GDP.

· Both cAMP and cGMP are converted to AMP and GMP by their respective phosphodiesterases.

· Some pathways that involve Ca²⁺ intersect with those involving cAMP. Some pathways diverge, others converge, and some do both.

· Caffeine in coffee is a stimulant, in part, because it inhibits cAMP phosphodiesterase.

· The signaling pathways are like switches in sophisticated electrical systems. Complex cellular behaviors can result from the interactions of many simple switching systems.

Effects

· Effects of signaling are manifest in the opening of membrane channels, changes in enzyme activity, and differences in gene transcription.

Membrane channels are opened

· Sense of smell in mammals is an example of a sensory system.

· Some mammals have as many as 1,000 genes that code for odorant receptors.

· Considering current estimates for the total number of genes in a human range from around 50,000 to 100,000 genes, the possibility that a species of mammal has 1/60 of all their genes dedicated for the detection of odor is rather astounding!

· Each of the thousands of nerve cells present in the nose expresses just one of these receptors.

· When an odorant molecule binds to its receptor, a G protein becomes activated. (See Figure 15.16.)

· The activated G protein subunit causes adenylyl cyclase to make the second messenger, cAMP.

· The cAMP binds to ion channels, causing them to let in Na⁺.

· The change in Na⁺ ion concentration stimulates the neuron to send a signal to the brain, which perceives the signal as a scent.

· Some odor molecules bind to more than one type of odorant receptor. This provides a means to detect and distinguish enormous numbers of different odors.

Enzyme activities are changed

· The effects of epinephrine on liver cells are an example of signal transduction resulting in altered enzyme activity. (See Figure 15.17.)

· The binding of epinephrine to a G protein-linked receptor results in synthesis of cAMP. cAMP in turn initiates a series of kinase reactions.

· The end effects of this signal transduction pathway include the alteration of two enzymes:

· Glycogen synthase is deactivated by phosphorylation. When active, this enzyme catalyzes the joining of glucose molecules into glycogen for storage.

· Deactivation of this enzyme therefore slows storage of glucose.

· Glycogen phosphorylase is activated. This enzyme catalyzes the release of glucose molecules from glycogen.

Different genes are transcribed

· Ras signaling pathways end in the nucleus (refer to Figure 15.11).

· The final protein kinase phosphorylates a DNA binding protein called AP-1.

· This activated AP-1 protein now can bind to DNA and influence gene transcription.

· Finally, a number of genes involved with cell division are transcribed.

· Lipid-soluble steroid hormones bind to receptors in the cytoplasm, which then influence gene transcription.

· In plants, light acts as a signal to begin chloroplast formation.

· Bright light activates phytochrome, which then binds to cytoplasmic regulatory proteins found in the cytoplasm.

· These can then move to the nucleus, bind DNA, and influence gene transcription, leading to the synthesis of important chloroplast proteins.

Direct Intercellular Communication

· Some cells send signals directly from their interior to the interior of adjacent cells.

· This transfer occurs because their cytoplasms are coupled together with specialized structures called junctions and plasmodesmata.

Animal cells communicate by gap junctions

· Gap junctions couple together animal cells. (See Figure 15.18. The Instructor’s Resource CD-ROM includes a freeze-fracture TEM of one side of a gap junction.)

· Gap junctions are complexes of proteins that generate pores in membranes. These protein complexes couple the plasma membrane of one cell with adjacent cells that also have these proteins.

· The pores can be gated and are either open or closed.

· Each gap junction is made up of numerous channel-generating proteins called a connexon.

· Each connexon is made up of six small snap-together subunits called connexins.

· The pore is small relative to macromolecules, but large enough for cAMP-size molecules to pass.

· Ca²⁺ molecules can also pass through the pore.

· In the developing mammalian egg, for example, the surrounding granulosa cells form gap junctional complexes with the egg.

· Some evidence exists that cAMP levels maintained by the granulosa control the state of development of the egg.

Plant cells communicate by plasmodesmata

· In plant cells, communication directly from the cytoplasm of one cell to another is through plasmodesmata. (See Figure 15.19. The Instructor’s Resource CD-ROM includes images of plasmodesmata in Chapters 5, 15, and 34.)

· These are membrane-lined bridges spanning the thick cell walls between adjacent cells.

· Generation of plasmodesmata involves fusion of adjacent plasma membranes to make the pore or connection.

· The pore is about 3 times as large as the ones in gap junctions.

· However, the space for molecular traffic is usually about the same as in gap junctions, approximately 1.5 nm.

· Therefore, only small molecules generally move through plasmodesmata.

· A tube called the desmotubule fills most of the pore.

· Plasmodesmata are important to C₄ plants, helping them to move fixed carbon between mesophyll and bundle sheath cells.

· Plasmodesmata pore size can be regulated. Some very large proteins have been found to move through them.

· These proteins, as well as RNA viruses, are able to get through temporarily enlarged pores.

Photographs on the Instructor’s Resource CD-ROM include a gap junction (in Chapter 5), plasmodesmata, and the series showing a wave of calcium ions through a fertilized starfish egg (Figure 15.14).