Biotecnologia

ARTICLE IN PRESS

Progress in Biophysics & Molecular Biology 83 (2003) 101–130

Review

G-proteins as transducers in transmembrane signalling
Stefan Offermanns*
Institute of Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany

Abstract The G-protein-mediated signalling system has evolved as one of the most widely used transmembrane signallingmechanisms in mammalian organisms. All mammalian cells express G-protein-coupled receptors as well as several types of heterotrimeric G-proteins and effectors. G-protein-mediated signalling is involved in many physiological and pathological processes. This review summarizes some general aspects of G-protein-mediated signalling and focusses on recent data especially from studies in mutant mice whichhave elucidated some of the cellular and biological functions of heterotrimeric G-prtoteins. r 2003 Elsevier Ltd. All rights reserved.

Contents 1. 2. 3. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102

The G-protein-mediated signalling system . . . . . . . . . . . . . . . . . . . . . . . . . . . 103 2.1. Receptor-independent modulation ofG-protein activity . . . . . . . . . . . . . . . . . 108 G-protein a-subunits and 3.1. The Gai/o-family . 3.2. The Gaq -family . . 3.3. The Ga12 -family . 3.4. The Gas -family . . bg-complexes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110 111 113 113 114 114 114 115 115 116

4.

Modulation of neuronal functions through G-protein-mediated 4.1. The role of Gi/o in CNS function . . . . . . . . . .. . 4.2. Gz function in the nervous system . . . . . . . . . . . . 4.3. Golf function in the nervous system . . . . . . . . . . . 4.4. Gq/11 mediated signalling in the CNS . . . . . . . . . .

signalling . . . . . . . . . . . . . . . . . . . . . . . . .

*Fax: 49-6221-54-8549. E-mail address: stefan.offermanns@urz.uni-heidelberg.de (S. Offermanns). 0079-6107/03/$ - see front matter r 2003Elsevier Ltd. All rights reserved. doi:10.1016/S0079-6107(03)00052-X

ARTICLE IN PRESS
102 5. S. Offermanns / Progress in Biophysics & Molecular Biology 83 (2003) 101–130 Regulation of heart function through G-proteins . . . . . . . . . . . . . . . . . . . . . . . 116 5.1. G-protein-mediated signalling in autonomous control of heart function . . . . . . . . . 116 5.2. The role of Gq/G11-mediatedsignalling pathways in myocardial hypertrophy . . . . . . 118 Function of Gi-type G-proteins in the immune system . . . . . . . . . . . . . . . . . . . . . G-protein-mediated signalling in sensory systems 7.1. Olfactory system/pheromone system . . . . 7.2. Visual system . . . . . . . . . . . . . . . . 7.3. Gustatory system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118 120 120 120 121 121 123 123

6. 7.

8. 9.

G-proteins in platelet activation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

References .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1. Introduction Numerous hormones, neurotransmitters or sensory stimuli exert their biological effects through transmembrane receptors which couple to heterotrimeric guanine nucleotide binding proteins (Gproteins). G-proteins in turn regulate the activity of various effectors like enzymes and ion...