Authors: Hawkes, C.¹; Amritraj, A.¹; MacDonald, R.²; Jhamandas, J.³; Kar, S.⁴

Source: Molecular Neurobiology, Volume 35, Number 3, June 2007 , pp. 329-345(17)

Publisher: Humana Press

Abstract:

The G protein-coupled receptor (GPCR) family represents the largest and most versatile group of cell surface receptors. Classical GPCR signaling constitutes ligand binding to a seven-transmembrane domain receptor, receptor interaction with a heterotrimeric G protein, and the subsequent activation or inhibition of downstream intracellular effectors to mediate a cellular response. However, recent reports on direct, receptor-independent G protein activation, G protein-independent signaling by GPCRs, and signaling of nonheptahelical receptors via trimeric G proteins have highlighted the intrinsic complexities of G protein signaling mechanisms. The insulin-like growth factor-II/mannose-6 phosphate (IGF-II/M6P) receptor is a single-transmembrane glycoprotein whose principal function is the intracellular transport of lysosomal enzymes. In addition, the receptor also mediates some biological effects in response to IGF-II binding in both neuronal and nonneuronal systems. Multidisciplinary efforts to elucidate the intracellular signaling pathways that underlie these effects have generated data to suggest that the IGF-II/M6P receptor might mediate transmembrane signaling via a G protein-coupled mechanism. The purpose of this review is to outline the characteristics of traditional and nontraditional GPCRs, to relate the IGF-II/M6P receptor's structure with its role in G protein-coupled signaling and to summarize evidence gathered over the years regarding the putative signaling of the IGF-II/M6P receptor mediated by a G protein.

Keywords: G protein-coupled receptor; IGF-II/MGP; Heterotrimeric G protein

Document Type: Research article

DOI: http://dx.doi.org/10.1007/s12035-007-0021-2

Affiliations: 1: Department of Psychiatry, Centre for Alzheimer and Neurodegenerative Research, University of Alberta, Edmonton, AB, Canada, T6G 2B7, 2: Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA, 3: Department of Medicine (Neurology), Centre for Alzheimer and Neurodegenerative Research, University of Alberta, Edmonton, AB, Canada, T6G 2B7, 4: Department of Psychiatry, Centre for Alzheimer and Neurodegenerative Research, University of Alberta, Edmonton, AB, Canada, T6G 2B7, Email: skar@ualberta.ca

Publication date: 2007-06-01

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