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Qualitative and Quantitative Characterization of the Distribution of G-Protein α Subunits in Mammals

  • Chapter
GTPases in Biology II

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 108 / 2))

Abstract

A large family of heterotrimeric guanine nucleotide binding proteins (G-proteins) have now been identified by a combination of biochemical and molecular biological approaches (Simon et al. 1991; Kaziro et al. 1991). In a number of cases the proteins have been purified essentially to homogeneity, and much is known about the receptor and effector systems which interact with them. However, in a number of other examples the protein has yet to be identified, and little more than information on the predicted protein sequence and tissue distribution of corresponding mRNA is currently known (Strathmann and Simon 1991). Details of the tissue and cellular distribution of these G-protein polypeptides (Milligan 1989) would clearly assist in efforts to delineate their likely functions. For example, knowledge of the tissue distribution of relevant mRNA and of the CNS sites of action of pharmaceutical agents assisted in the identification of an orphan G-protein linked receptor cDNA as one encoding a cannabinoid receptor (Matsuda et al. 1990). While it is generally accepted that the central role for heterotrimeric G-proteins is in the transmission of information across the limiting external membrane of a cell, it is now clear that the subcellular location of G-proteins is not restricted to the plasma membrane (Milligan 1989; Ercolani et al. 1990; Burgoyne 1992; Ktiskatis et al. 1992). For example, it has been reported that in LLC-PK1 cells Gi3α displays a distinct perinuclear pattern of immunostaining suggesting location on the Golgi membranes (Ercolani et al. 1990), and a similar pattern of Gi3α immunoreactivity has been noted in BALB/c3T3 fibroblasts (LaMorte et al. 1992). A Gi-like polypeptide has also been reported in rat liver nuclei (Takei et al. 1992), and agonist activation of receptors can, at least in certain circumstances, alter the cellular distribution and/or amounts of G-proteins (McKenzie and Milligan 1990b; Green et al. 1992; Negishi et al. 1992; see Milligan and Green 1991 for review). Knowledge of the cellular localization of G-proteins may thus assist in the identification of further functions for these polypeptides (Ercolani et al. 1990; Ktiskatis et al. 1992; see Burgoyne 1992 for review). Furthermore, at least in certain polarized cells, G-proteins are not evenly distributed in the plasma membrane (Ali et al. 1989; Gabrion et al. 1989; Ercolani et al. 1990; van den Berghe et al. 1991), and the possibility of a regulatory role for cytoskeletal control of G-protein distribution in a cell is gaining credence (Wang et al. 1990).

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  1. G. Milligan
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Editors and Affiliations

  1. Baylor College of Medicine, Department of Medicine Cell Biology and Experimental Therapeutics, Houston VA Medical Center, Room 3C-385, 2002 Holcombe Boulevard, Houston, TX, 77030, USA

    Burton F. Dickey M.D.

  2. Department of Cell Biology, Molecular Physiology and Biophysics, Medicine and Neurosciences, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA

    Lutz Birnbaumer Ph.D.

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Milligan, G. (1993). Qualitative and Quantitative Characterization of the Distribution of G-Protein α Subunits in Mammals. In: Dickey, B.F., Birnbaumer, L. (eds) GTPases in Biology II. Handbook of Experimental Pharmacology, vol 108 / 2. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-78345-6_4

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