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3 SIGNAL TRANSDUCTION
The evolution of multicellular organisms necessitated the development of mechanisms to tightly coordinate theactivities among cells. Such
is fundamental to all biological processes, ranging from the induction of embryonic development to the integration of physiological responses in the face of environmental challenges. As our understanding of cellular and molecular physiology has increased, it has become evident that all cells canreceive and process information. External
such as odorants, chemicals that reflect metabolic status, ions,hormones, growth factors, and neurotransmitters can all serve as
linking neighboring or distant cells. Even external signals that are not considered chemical in nature (e.g., light and mechanical or thermalstimuli) may ultimately be transduced into a chemical messenger. Most chemical messengers interact with specific
cell surface receptors
and trigger a cascade of secondary events, including the mobilization of diffusible intracellular
that mediate the cell's response to that stimulus. However, hydrophobic messengers,such as steroid hormones and some vitamins, can diffuse across the plasma membrane and interact with
cytosolicor nuclear receptors
. It is now clear that cells use a number of different, often intersecting intracellular signalingpathways to ensure that the cell's response to a stimulus is tightly controlled.
MECHANISMS OF CELLULAR COMMUNICATION
Cells Can Communicate with One Another by Chemical Signals
Early insight into signal transduction pathways was obtained from studies of the endocrine system. The classicdefinition of a
a substance that is produced in one tissue or organ and released into the blood and carried to other organs (targets), where it acts to produce a specific response
. The idea of endocrine or ductless glandsdeveloped from the recognition that certain organs-such as the pituitary, adrenal, and thyroid gland-can synthesizeand release specific chemical messengers in response to particular physiological states. However, many other cellsand tissues not classically thought of as endocrine in nature also produce hormones. For example, the kidneyproduces 1,25-dihydroxyvitamin D
, and the salivary gland synthesizes nerve growth factor.It is now recognized that intercellular communication can involve the production of a "hormone" or chemical signal byone cell type that acts in any (or all) of three ways, as illustrated in Figure 3-1: on distant tissues (
), on aneighboring cell in the same tissue (
), or on the same cell that released the signaling molecule (
).For paracrine and autocrine signals to be delivered to their proper targets, their diffusion must be limited. Thisrestriction can be accomplished by rapid endocytosis of the chemical signal by neighboring cells, its destruction byextracellular enzymes, or its immobilization by the extracellular matrix. The events that take place at theneuromuscular junction are excellent examples of paracrine signaling. When an electrical impulse travels down anaxon and reaches the nerve terminal (Fig. 3-2), it stimulates release of the neurotransmitter acetylcholine (ACh). Inturn, ACh transiently activates a ligand-gated cation channel on the muscle cell membrane. The resultant transientinflux of Na
causes a localized positive shift of
(i.e., depolarization), initiating events that result in propagation of an action potential along the muscle cell. The ACh signal is rapidly terminated by the action of acetylcholinesterase,which is present in the synaptic cleft. This enzyme degrades the ACh that is released by the neuron.
Soluble Chemical Signals Interact with Target Cells by Binding to Surface or Intracellular Receptors
Four types of chemicals can serve as extracellular signaling molecules:
, such as epinephrine;
, such as angiotensin II and insulin;
, including aldosterone, estrogens, and retinoic acid; and other
, such as amino acids, nucleotides, ions (e.g., Ca
), and gases (e.g., nitric oxide).
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Figure 3-1 Modes of cell communication.