Hormone-induced subcellular redistribution of trimeric G proteins.
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 a 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.
Svoboda
P
P
Institute of Physiology, Academy of Sciences of the Czech Republic, Prague. svobodap@biomed.cas.cz
Novotny
J
J
D000818:Animals; D016477:Artifacts; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D006728:Hormones / Q000494:pharmacology*; D006801:Humans; D021122:Protein Subunits; D021381:Protein Transport / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000378:metabolism; D012995:Solubility
D006728:Hormones; D021122:Protein Subunits; D011956:Receptors, Cell Surface; D020962:Heterotrimeric GTP-Binding Proteins