Mechanisms of Cell Communication To make a multicellular organism, cells must communicate, just as humans aust communicate if they are to organize themsdlves into 2 complex saciety. ‘mission of chemical signals across the space between one cell and anather. Complex intracellular mechanisms are needed tm contral which signals are ‘emitted at what time and to enable the signal-receiving cell to interpret those signals and use them to guide its behavior. According to the fore record, saphis- isma resembling present-day procaryotes i ‘bout 25 billion years. The long delay may reflect the difficulty of evolving the Tanguage systems of animal, plant, and fungal cells—the machinery that would signaling pathways they activate. focus ofthe chapter is on animal cells, but we end by considering the special fea- tures of cell communication in plants. GENERAL PRINCIPLES OF CELL COMMUNICATION Long before multicellular organisms appeared an Earth, unicellular orgarisms‘The large numbers of signal proteins, receptors, and intracellslar signaling, proteins used by animals can be grouped ime a much smaller number of protein families, most of which have been highly conserved in evolution. Flies, worms, aandmammals all use essentially similar machinery for cell communication, and many of the key components and signaling pathways were firt discovered through analysis of mutations in Drosophila and €.eleparc Extracellular Signal Molecules Bind to Specific Receptors (Celle irs multicellular animals communicate by means of hundreds of kinds of signal molecules. These include proteins, small peptides, amino acids, Figaro 15-1 A simple nace ‘Spesing petesy ord bya erollsr sept moti, Te Spal tmotcus tsny onc toa recptor prota that scnbodin bo pasa fanbrana of th go cell and arts one oor scam erm ya potare Peay cre or more ii etcar agrang protest fhe acy of oer potas snd thory bana the call crete en pepe |‘ucieatides, steroids, retinoids, faty acid derivatives, and even dissolved gases such a: nitric oxide and carhem moaoxide, Mort of these signal molecules are released inta the extracellular space by exocytosis fram the signaling cell = discussed in Chapter 13. Some, however, ae emitted by diffusion through the signaling cells plasma membrane, whereas others are displayed on the external surface of the cell and remain attached ta it, providing 3 signal to other cells, only when they make contact. Transmembrane proteins may be used for sig- ‘naling in this way; or their extracelialar Garains may be released fromm the sig- ‘naling cells surface by proteolytic cleavage and then actat a distance Regandless af the nature ofthe signal, the target cellresponds by means of a receptor, which specifically binds the signal molecule and then initiates a respoeoe in the target cell The extracellular signal malecules often act at very low concentrations (typically = 10 M), and the receptors that recognize them In most cases, the receptors are transmembrane proteins oa the target cell surface. When these proteins bind an extracellular signal molecule (a Ligand), they hecome activated and generate various intracellular signals that slter the ‘behavior of the cell In other cases, the receptar peoteins are inside the target ‘cell, and the signal molecule hax to enter the cello bind to theme this requires ‘that the signal malecule be sufficiently small and kydrophabic to diffuse across ‘the target cells plasma membrane (Plgure 15-3). Extracellular Signal Molecules Can Act Over Either Short ar Long Distances Many signal molecules remain bound to the surface ofthe signaling cell nd influence only cells that contact it (Plgure 15-44. Sach cantact-dependent atg- naling is expecially important during development and in immune responses. Contact.dependert signaling during development can sometimes aperate ove? ‘relatively lage distances, where the communicating cells extend long processes tg make contact with one another I most cases. however, signaling cells secrete signal molecules into the extracellular fluid. The secreted molecules may becerried far field to acton dis- tant target cells, or they may act a5 local mediators, affecting oniy cells in the localervitonrment ofthe sigaling.cell The latter process is called paracrine stg. ‘nabing (Figure 15-48). Usually the signaling and target cefls in paracrine signal ing are of different celltypes, bt cells may alsa prodiuce signals that they them- aches respond tor this is referred to ax autocrine signaling. Cancer cell, for ‘example, often use this siraiegy to stimulsie their own survival and proliferation. For paracrine signals to act only locally, the secreted molecules must nat be Allowed ts éifuse ton far; for this reason they are often rapidly taken up by ‘neighboring target celle, etroyed by exizacellular enzymes, or iramobilzed by the extracellular mairs. Heparan sulfate proieogtyoans (discussed in Chapter 19), either in the extracellular matrix ar stzached to cell surfaces, often play a pari in localizing the action of socreted signal proteins, They contain loag, ‘alysaccharide side chains that bind the signal proteins and immobilize ther. ‘They may also control che stability ofthese proteins, ther transport through the ‘extracellular space, o their interaction with cell-surface receptors. Secreted pro- tein antagonists alzo affect the distance aver which a paracrine signal protein acts. These antagonists bind io either the signal moleculeitself or its cell-surface ‘recepenr and biock its ativity,and they play an important par in restricting the effective range of secreted signal proteins that infuence the developmental ‘decisions thal eoibryonic cells make (discussed in Chapter 22). Large, cormples, multicellular organisms need long-range signaling mecha- ‘nism to coordinate the behavior of cells in remote parts ofthe body. Ths, they have evolved cell types specialized for intercellular communication over large distances, The most sophisticated of these are nerve cells, or neurons, which {typically extend long branching processes (axons) that enable them to contact large cells far away, where the processes terminate at the specislized sites of te ceuummacearcerroes perenne = = Rage{ { i Ht ! © signal trancission known ar chomsical qrapss: When activated bystrash oem theeavironment or from other nerve cell the neuron sendselectricalimpules {acti potential) rapidly along its mar: when such an impulse reaches the synapse atthe cod of the zane. tigger scercion ofa chemical signal hae arts ‘ssa neurotranemtier. The tghily ongiized stracure of the synapse ensures {Gat the neurotransmitter is delivered speciScally tp receptors oa the potty smapic target cell (igure 15-1C]. The delat of te symaple sgmaling process se discunsed in Chapter 11. ‘A quite different strategy for signaling ver long distances makes use of endocrine celle. These scrote the signal molecule, called hormones, so the ‘loodstream, which caries the molecules far and wide, allowing them to act on target cells hat may be anywhere in the body (Pagure I-40). ‘igure 15-5 compares the machanisms that allow endocrine cell and nerve cls te coordinate cell behavior over lang distances in animals. Because ‘endocrine signaling relics on difurion andblood flaw, itisreaively slow Syesp- fic signaling by contrast is much faster, as wells more precise Nerve cells cam traramit tcrmation aver lang distances by electrical emotes that travel at speeds of up to 100 meters per sscond: ance released from a nerve terminal, neurotransmrinc hast diffuse less then 100 nm to dhe target cells process that {kes few hana mifisecond. Another diffrence between endvcrine and symap- tie signaling shal whereas hormones are greatly cised iy he bloodsercam ard interstitial Fal and therefore must he ableto act stwery low concentration (p- ically < 10-* My, neurotransmitter: are diluted much les and cam achieve high Siatine surement, lr comple eabeat in 1048 Comepand ingly neurotransmitier receptors have a relacively law aii for thee igund, wich means tha the ncuredtanstis can dissociate rapidly fom the reopen tw help terminatea response. Moreover afer ts release fam t nerve terminal a feuroranamier i quichiy removed um the synaptic lef herby speci Inpro eneymes that desry hr by specific membrane ranspot proteins ‘welen zo ten ated at sey Mom oumeal cll nog ENcoCrnE Spang depen on ender cals, ‘sven sce horTona i at loncsneam for dtbutonthrouspout me rhe aa ype ok ay Way ot‘gr SST contrast nett andor be eerste ot ‘Sag range sgnaing compra cnescane rte ndsan ats ‘nectngen beara aco ten iy spa {rte op nara cert nso cot mt emmorsife communes parca ws gt ct See ‘Son otvea ha sane soocrahm tr sds comics M3 Space manna tensorial eres amar aoe ‘Baltes coon to tpt catty the ers ‘seapee ba orp ‘emons ane ge as Ps cera dn mae again ‘ah ipocrey resto tarp conor tera ers all Srotmespane wigtcem tat ons aay orate ca ‘Tats n yrapte communes wen arene cal opera Seuantmaa ied nom na ial enh ‘ae ‘Seuransmimar ac nspancana mo rng atc red at (nc mu gt co tho a ‘that pump it back into either the nerve ternal or neighboring gil cll. Tis, “synaptic signaling isrmuch more precise than endocrine signaling, bath ime sand in space. “The speed of arecponse ta an extracellular signal depends nat only on the smechaniarn of signal delivery but alea on the nature ofthe target cellrresporse, When the response requires only changes in proteins already present inthe col i¢-can occur tery rapidly: an allosteric change in a neurotranemtier gated jam ‘channel (discussed in Chapter 11), for example. can aller the plasma membeane ‘esr pom inmisecond and responses hat depend ally om rosin [phosphorylation can occur within seconds. When the Ehange gene mppesion snd dar satharecl new poses, However ara ally requires many rninutes or hours, regardless of the mode of signal delivery (Figure 15-5. ‘Figur 166 Ertracllutar signa can act slowly or rply to cango the bhava 3 target ‘call Cartan typer tsa ee ponmon sch 3 resend cll growth an iveon cs [hanges mgonsaprotinn snd us syrinase of row prc boy tore ocr ‘fies sang star ambou cr more Gir spon such archangel ‘omen erent meetin ange nae pin ast sen arg ee or eee am enema ee