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Signal Transduction - Basic Mechanisms and Types of Receptors.

BY: Sandhya Anand | Category: Others | Submitted: 2011-04-19 08:22:37
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Article Summary: "The article describes the components of the signal transduction pathways and the major types of receptors involved in signal transduction..."

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Signal transduction pathways allow the cells to sense and respond to external stimuli. Signals are sensed by receptors, and changed by transducers which are passed on to effectors which trigger the final response.

Components of the signal transduction pathways

a. Signals can exert their effects from outside the cell or be needed to enter the cell in order to elicit a response. Those that enter the cell include steroids, retinoids, thyroid hormone and Vitamin D etc. Generally lipohilic molecules having smaller size can cross the plasma membrane easily and hence act as intracellular signals. Signals are sensed by target cells.

b. Receptors get activated upon sensing the signal. They undergo structural changes which activates the whole pathway. For signal molecules which enter the cell, there are internal receptors. External receptors are found on the cell surface. They transmit the signal via activation of signaling pathways. The same signal molecule can elicit different responses from different cells due to receptor diversity. Cytosolic receptors are soluble in nature and sense intracellular signals. Transmembrance receptors span the cell membrance sensing extracellular signals and triggering responses inside the cell.

Based on the mechanism of action, transmembrance receptors can be classified into three types.
1. Enzyme coupled receptors which activates an enzyme usually within the receptor itself eg: Phospholipase C, Tyrosine kinases.
2. Ion channeled receptors are those which trigger responses via an ion channel. Eg: Acetyl choline receptor.
3. G-protein coupled receptors are linked with G-protein which inturn activates the other intracellular enzymes through second messengers such as cAMP, Calcium ion etc.

c. Transducers convert the form of signal, amplify or integrate those from multiple pathways.
d. Amplifiers: increase the signal strength. One molecule of signal is amplified into numerous outgoing signals (secondary signals). Examples include G-proteins, kinases, cyclases etc. Multiple amplifications in a signal transduction pathway makes a cascade.
e. Integrators integrate multiple signals from different pathways to a common effector molecule. Eg: phosphorylase kinase gets activated by Calcium ion as well as cAMP molecule. When either of the signal molecule is in abundance or in the presence of both molecules, the enzyme gets activated to a common response.
f. Effectors are triggering the result or final response. Just as integrators can sense multiple signals, same signal can respond and trigger multiple pathways. This is possible due to the presence of different effector molecules.
g. Inhibitors block the signaling pathways. The effect of presence of an inhibitor is the same as removal of the signal molecule/ inactivation of signaling. Eg: Phosphatases inhibit kinases; Cyclic nucleotides get hydrolyzed by phosphodiesterases;

Characters of signaling

a. Specificity - Signal molecules are highly specific to the receptor. The signal-receptor binding is unique for each signal.
b. Amplification of signals into secondary signals is often found in enzyme linked signal transduction pathways. The increase is usually geometric in nature forming a cascade of metabolic responses.
c. Adaptation - Once the receptor is bound to a signal, it triggers a change that desensitizes the receptor to further signaling molecules. This response may either remove the receptor from the surface or shut down the receptor.
d. Integration- When there are two or more signals of antagonistic metabolic functions, the cumulative response of the signal transduction pathway is the result of integration of such signals from multiple pathways.

Types of receptors

Based on the mechanism of action, there are different types of receptors
a. Gated ion channel receptors are those which open and close in response to the concentration of the signal molecule. In some cases it is dependent on the membrane potential as in acetyl choline receptor.
b. Receptors with enzymatic activity. They trigger enzymatic responses in the cell. Signals are sensed by the extra cellular domain of the receptor and the intracellular domain of the receptor triggers a response by activating a specific enzyme usually a part of the receptor.
c. Steroid receptors are nuclear receptors which bind to the signal molecules to regulate the gene expression patterns. Due to their small size and lipophilic nature, the signal molecules can enter the cell and diffuse through the membrane to bind to these receptors triggering a response.
d. Adhesion receptors bind extracellular signals and change their conformation and trigger responses in the cytoskeleton. They allow the cells to migrate, proliferate etc. They act as transducers also in developmental programs and pathways. These play important roles in regulation of embryogenesis, organogenesis, and cell proliferation in response to injury in regenerating tissues. Examples include integrins, cadherins, selectins etc.
e. Serpentine receptors are transmembrane receptors which bind to extracellular signals; activate a GTP-binding protein (G-protein) which inturn activates the enzyme to trigger the production of intracellular second messengers.
f. Receptors without enzymatic activity depend on intracellular protein kinases for triggering the response. The final effect is some times mediated though enzyme cascades involving protein kinases. These can even cause changes in gene expression.

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