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Communication, Integration, and Homeostasis

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Communication, Integration, and Homeostasis Communication, Integration, and 6 Homeostasis Cell-to-Cell Communication Gap Junctions Create Cytoplasmic Bridges Contact-Dependent Signals Require Cell-to-Cell Contact Paracrine and Autocrine Signals Carry Out Local Communication Long-Distance Communication May Be Electrical or Chemical Cytokines May Act as Both Local and Long-Distance Signals Signal Pathways Receptor Proteins Are Located Inside the Cell or on the Cell Membrane Membrane Proteins Facilitate Signal Transduction Receptor-Enzymes Have Protein Kinase or Guanylyl Cyclase Activity Most Signal Transduction Uses G Proteins Many Lipophobic Hormones Use GPCR-cAMP Pathways G Protein–Coupled Receptors Also Use Lipid-Derived Second Messengers Integrin Receptors Transfer Information from the Extracellular Matrix The Most Rapid Signal Pathways Change Ion Flow Through Channels Future progress Novel Signal Molecules in medicine Calcium Is an Important Intracellular Signal will require a Gases Are Ephemeral Signal Molecules quantitative Some Lipids Are Important Paracrine Signals understanding Modulation of Signal Pathways of the many One Ligand May Have Multiple Receptors interconnected Receptors Exhibit Saturation, Specifi city, and Competition networks of Up- and Down-Regulation Enable Cells to Modulate Responses molecules that Cells Must Be Able to Terminate Signal Pathways comprise our cells Many Diseases and Drugs Target the Proteins of Signal Transduction and tissues, their interactions, and Homeostatic Refl ex Pathways their regulation. Cannon’s Postulates Describe Regulated Variables and Control Systems Long-Distance Pathways Maintain Homeostasis — Overview of the NIH Control Systems Vary in Their Speed and Specifi city Roadmap, 2003 Complex Refl ex Control Pathways Have Several Integrating Centers Background Basics Homeostasis Nucleotides Cell junctions Extracellular matrix Endocrine glands Membrane structure Membrane proteins Diff usion Exocytosis Microarray 184 Communication, Integration, and Homeostasis n 2003 the United States National Institutes of Health em- extracellular fluid. Chemical signals are responsible for most barked on an ambitious project to promote translation of communication within the body. Th e cells that respond to electri- I basic research into new medical treatments and strategies cal or chemical signals are called target cells , or targets for short. for disease prevention. Contributors to the NIH Common Fund Our bodies use four basic methods of cell-to-cell commu- Programs ( http://commonfund.nih.gov ) are compiling infor- nication ( Fig. 6.1 ). Local communication includes (1) gap mation on biological pathways in an eff ort to understand how junctions, which allow direct cytoplasmic transfer of electrical cells communicate with one another and maintain the body in and chemical signals between adjacent cells; (2) contact- a healthy state. In this chapter, we examine the basic patterns dependent signals, which occur when surface molecules on one of cell-to-cell communication and see how the coordination of cell membrane bind to surface molecules on another cell’s mem- function resides in chemical and electrical signals. Each cell in brane; and (3) chemicals that diff use through the extracellular the body can communicate with most other cells. To maintain fluid to act on cells close by. Long-distance communication homeostasis, the body uses a combination of simple diff usion (4) uses a combination of chemical and electrical signals carried across small distances; widespread distribution of molecules by nerve cells and chemical signals transported in the blood. through the circulatory system; and rapid, specifi c delivery of A given molecule can function as a signal by more than one messages by the nervous system. method. For example, a molecule can act close to the cell that released it (local communication) as well as in distant parts of Cell-to-Cell Communication the body (long-distance communication). In recent years the amount of information available about cell- Gap Junctions Create Cytoplasmic Bridges to-cell communication has mushroomed as a result of advances in research technology. Signal pathways that once seemed fairly Th e simplest form of cell-to-cell communication is the direct simple and direct are now known to be incredibly complex net- transfer of electrical and chemical signals through gap junctions, works and webs of information transfer. In the sections that fol- protein channels that create cytoplasmic bridges between adja- low, we distill what is known about cell-to-cell communication cent cells ( Fig. 6.1 a). A gap junction forms from the union of into some basic patterns that you can recognize when you en- membrane-spanning proteins, called connexins, on two adjacent counter them again in your study of physiology. cells. The united connexins create a protein channel, or con- 6 By most estimates the human body is composed of about nexon , that can open and close. When the channel is open, the 75 trillion cells. Th ose cells face a daunting task—to communi- connected cells function like a single cell that contains multiple cate with one another in a manner that is rapid and yet conveys a nuclei (a syncytium ). tremendous amount of information. Surprisingly, there are only When gap junctions are open, ions and small molecules such two basic types of physiological signals: electrical and chemical. as amino acids, ATP, and cyclic AMP diffuse directly from the Electrical signals are changes in a cell’s membrane potential. cytoplasm of one cell to the cytoplasm of the next. Larger molecules Chemical signals are molecules secreted by cells into the cannot pass through gap junctions. In addition, gap junctions are the only means by which electrical signals can pass directly from cell to cell. Movement of molecules and electrical signals through RUNNING PROBLEM gap junctions can be modulated or shut off completely. Gap junctions are not all alike. Scientists have discovered Diabetes Mellitus: A Growing Epidemic more than 20 diff erent isoforms of connexins that may mix or It is 8:00 A.M. and Marvin Garcia, age 20, is hungry. He came to match to form gap junctions. Th e variety of connexin isoforms his family physician’s offi ce before breakfast to have a fasting allows gap junction selectivity to vary from tissue to tissue. blood glucose test as part of a routine physical examination. In mammals, gap junctions are found in almost every cell type, In this test, blood is drawn after an overnight fast, and the including heart muscle, some types of smooth muscle, lung, glucose concentration in the blood is measured. Because he liver, and neurons of the brain. knows he is in good condition, Marvin isn’t worried about the results. He is surprised, then, when the nurse practitioner in the doctor’s offi ce calls two days later. “Your fasting Contact-Dependent Signals Require blood sugar is a bit elevated, Marvin. It is 150 milligrams Cell-to-Cell Contact per deciliter, and normal is 110 or less. Does anyone in your family have diabetes?” “Well, yeah—my dad has it. What Some cell-to-cell communication requires that surface mol- exactly is diabetes?” ecules on one cell membrane bind to a membrane protein of an- other cell ( Fig. 6.1 b). Such contact-dependent signaling occurs in the immune system and during growth and development, such as when nerve cells send out long extensions that must grow from the central axis of the body to the distal (distant) ends of 185 Fig. 6.1 ESSENTIALS Communication in the Body Cell-to-cell communication uses chemical and electrical signaling to coordinate function and maintain homeostasis. LOCAL COMMUNICATION Receptor (a) Gap junctions form (b) Contact-dependent signals (c) Autocrine signals act on the same cell direct cytoplasmic require interaction between that secreted them. Paracrine signals connections between membrane molecules on are secreted by one cell and diffuse to adjacent cells. two cells. adjacent cells. LONG-DISTANCE COMMUNICATION Long-distance signaling may be electrical signals passing along neurons or chemical signals that travel through the circulatory system. Endocrine System Nervous System Electrical signal Target Blood cell Response Neuron Cell Cell (e) Neurotransmitters are chemicals secreted by neurons that diffuse Endocrine without with across a small gap to the target cell. cell receptor receptor Target cell No response Blood Response Neuron Cell Cell (d) Hormones are secreted by endocrine glands or cells into the blood. (f) Neurohormones are chemicals without with Only target cells with receptors for the hormone respond to the signal. released by neurons into the blood receptor receptor for action at distant targets. No response Response 186 Communication, Integration, and Homeostasis the developing limbs. Cell adhesion molecules (CAMs) first it is called a neurotransmitter ( Fig. 6.1 f). If a neurocrine acts known for their role in cell-to-cell adhesion, have now been more slowly as an autocrine or paracrine signal, it is called a shown to act as receptors in cell-to-cell signaling. CAMs are neuromodulator . If a neurocrine released by a neuron diff uses linked to the cytoskeleton and to intracellular enzymes. Th rough into the blood for distribution, it is called a neurohormone these linkages, CAMs transfer signals in both directions across ( Fig. 6.1 e). Th e similarities between neurohormones and clas- cell membranes. sic hormones secreted by the endocrine system blur the distinc- tion between the nervous and endocrine systems, making them Paracrine and Autocrine Signals Carry Out a functional continuum rather than two distinct systems. Local Communication Cytokines May Act as Both Local Local communication takes place through paracrine and auto- crine signaling. A paracrine signal { para −, beside + krinen, to and Long-Distance Signals secrete} is a chemical that acts on cells in the immediate vicinity Cytokines are among the most recently identifi ed communica- of the cell that secreted the signal. A chemical signal that acts on tion molecules. Initially the term cytokine referred only to pro- the cell that secreted it is called an autocrine signal { auto −, teins that modulate immune responses, but in recent years the self}.
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