Hormone-induced subcellular redistribution
of trimeric G proteins |
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Authors: | P Svoboda J Novotny |
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Institution: | (1) Institute of Physiology, Academy of Sciences of the Czech Republic, Videnska 1083, 142 00 Prague (Czech Republic), Fax + 420 2 475 2488, e-mail: svobodap@biomed.cas.cz, CZ;(2) Department of Physiology, Faculty of Natural Sciences, Charles University, 128 00 Prague (Czech Republic), CZ |
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Abstract: | Trimeric guanine nucleotide-binding proteins (G proteins) function as the key regulatory elements in a number of transmembrane
signaling cascades where they convey information from agonist-activated receptors to effector molecules. The subcellular localization
of G proteins is directly related to their functional role, i.e., the dominant portion of the cellular pool of G proteins
resides in the plasma membrane. An intimate association of G protein subunits with the plasma membrane has been well known
for a long time. However, results of a number of independent studies published in the past decade have indicated clearly that
exposure of intact target cells to agonists results in subcellular redistribution of the cognate G proteins from plasma membranes
to the light-vesicular membrane fractions, in internalization from the cell surface into the cell interior and in transfer
from the membrane to the soluble cell fraction (high-speed supernatant), i.e., solubilization. Solubilization of G protein
α subunits as a consequence of stimulation of G protein-coupled receptors (GPCRs) with agonists has also been observed in
isolated membrane preparations. The membrane-cytosol shift of G proteins was detected even after direct activation of these
proteins by non-hydrolyzable analogues of GTP or by cholera toxin-induced ADP-ribosylation. In addition, prolonged stimulation
of GPCRs with agonists has been shown to lead to down-regulation of the relevant G proteins. Together, these data suggest
that G proteins might potentially participate in a highly complex set of events, which are generally termed desensitization
of the hormone response. Internalization, subcellular redistribution, solubilization, and down-regulation of trimeric G proteins
may thus provide an additional means (i.e., beside receptor-based mechanisms) to dampen the hormone or neurotransmitter response
after sustained (long-term) exposure.
Received 31 August 2001; received after revision 31 October 2001; accepted 7 November 2001 |
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Keywords: | , Trimeric G proteins, subcellular distribution, solubilization, desensitization, |
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