We#discussed# regulation# from#the#context# of#inside# the# cellNow#we #add#a#dimension:# regulat ion#triggered#from#outs ide# the#cell :# signaling526 CHAPTER 16 Cell SignalingGENERAL PRINCIPLES OF CELL SIGNALINGInformation can come in a variety of forms, and communication fre-quently involves converting the signals that carry that information from one form to another. When you receive a call from a friend on your mobile phone, for instance, the phone converts the radio signals, which travel through the air, into sound waves, which you hear. This process of conversion is called signal transduction (Figure 16–2).The signals that pass between cells are simpler than the sorts of mes-sages that humans ordinarily exchange. In a typical communication between cells, the signaling cell produces a particular type of extracellular signal molecule that is detected by the target cell. As in human conver-sation, most animal cells both send and receive signals, and they can therefore act as both signaling cells and target cells. Target cells possess proteins called receptors that recognize and respond specifically to the signal molecule. Signal transduction begins when the receptor on a target cell receives an incoming extracellular signal and converts it to the intracellular signaling molecules that alter cell behavior. Most of this chapter is concerned with signal reception and transduc-tion—the events that cell biologists have in mind when they refer to cell signaling. First, however, we look briefly at the different types of extra-cellular signals that cells send to one another.Signals Can Act over a Long or Short RangeCells in multicellular organisms use hundreds of kinds of extracellular sig-nal molecules to communicate with one another. The signal molecules can be proteins, peptides, amino acids, nucleotides, steroids, fatty acid derivatives, or even dissolved gases—but they all rely on only a handful of basic styles of communication for getting the message across.In multicellular organisms, the most “public” style of cell-to-cell commu-nication involves broadcasting the signal throughout the whole body by secreting it into an animal’s bloodstream or a plant’s sap. Extracellular signal molecules used in this way are called hormones, and, in animals, the cells that produce hormones are called endocrine cells (Figure 16–3A). Part of the pancreas, for example, is an endocrine gland that produces several hormones—including insulin, which regulates glucose uptake in cells all over the body. (A)(B)ECB4 16.01/16.0110 µmFigure 16–1 Yeast cells respond to mating factor. Budding yeast (Saccharomyces cerevisiae) cells are normally spherical (A), but when they are exposed to an appropriate mating factor produced by neighboring yeast cells (B), they extend a protrusion toward the source of the factor. (Courtesy of Michael Snyder.)intracellularsignalingmolecule BOUTextracellular signal molecule A IN(A) (B)ECB4 e16.02/16.02soundOUTradiosignalINFigure 16–2 Signal transduction is the process whereby one type of signal is converted to another. (A) When a mobile telephone receives a radio signal, it converts it into a sound signal; when transmitting a signal, it does the reverse. (B) A target cell converts an extracellular signal molecule (molecule A) into an intracellular signaling molecule (molecule B).SignalingWhat#ar e#the#additional# pr inciples# we#need#to#under stand?Principle, 1: ,Multiple,spatial,dimensions,are,releva n t,to,signaling.Signaling527General Principles of Cell Signaling Somewhat less public is the process known as paracrine signaling. In this case, rather than entering the bloodstream, the signal molecules diffuse locally through the extracellular fluid, remaining in the neighborhood of the cell that secretes them. Thus, they act as local mediators on nearby cells (Figure 16–3B). Many of the signal molecules that regulate inflam-mation at the site of an infection or that control cell proliferation in a healing wound function in this way. In some cases, cells can respond to the local mediators that they themselves produce, a form of paracrine communication called autocrine signaling; cancer cells sometimes pro-mote their own survival and proliferation in this way. Neuronal signaling is a third form of cell communication. Like endocrine cells, nerve cells (neurons) can deliver messages over long distances. In the case of neuronal signaling, however, a message is not broadcast widely but is instead delivered quickly and specifically to individual tar-get cells through private lines. As described in Chapter 12, the axon of a neuron terminates at specialized junctions (synapses) on target cells that can lie far from the neuronal cell body (Figure 16–3C). The axons that extend from the spinal cord to the big toe in an adult human, for example, can be more than a meter in length. When activated by signals from the environment or from other nerve cells, a neuron sends electrical impulses racing along its axon at speeds of up to 100 m/sec. On reaching the axon terminal, these electrical signals are converted into a chemi-cal form: each electrical impulse stimulates the nerve terminal to release a pulse of an extracellular signal molecule called a neurotransmitter. The neurotransmitter then diffuses across the narrow (<100 nm) gap that separates the membrane of the axon terminal from that of the target cell, reaching its destination in less than 1 msec.A fourth style of signal-mediated cell-to-cell communication—the most intimate and short-range of all—does not require the release of a secreted molecule. Instead, the cells make direct physical contact through signal local mediatorsignalingcelltargetcellscellbodyneurotransmittersynapsenerveterminaltarget cellPARACRINESYNAPTICECB4 e16.03/16.03(B)(C)CONTACT-DEPENDENT(D)membrane-bound signalmoleculesignaling cell target cellneuronaxonendocrine cellhormonebloodstreamtarget cellENDOCRINE(A)receptortarget cellFigure 16–3 Animal cells use extracellular signal molecules to communicate with one another in various ways. (A) Hormones produced in endocrine glands are secreted into the bloodstream and are distributed widely throughout the body. (B) Paracrine signals are released by cells into the extracellular fluid in their neighborhood and act locally. (C) Neuronal signals are transmitted electrically