title: Heterotrimeric G protein signaling via GIV/Girdin: Breaking the rules of engagement, space, and time.
abstract: Canonical signal transduction via heterotrimeric G proteins is spatially and temporally restricted, that is, triggered exclusively at the plasma membrane (PM), only by agonist activation of G protein-coupled receptors (GPCRs) via a process that completes within a few hundred milliseconds. Recently, a rapidly emerging paradigm has revealed a non-canonical pathway for activation of heterotrimeric G proteins by the non-receptor guanidine-nucleotide exchange factor (GEF), GIV/Girdin. This pathway has distinctive temporal and spatial features and an unusual profile of receptor engagement: diverse classes of receptors, not just GPCRs can engage with GIV to trigger such activation. Such activation is spatially and temporally unrestricted, that is, can occur both at the PM and on internal membranes discontinuous with the PM, and can continue for prolonged periods of time. Here, we provide the most complete up-to-date review of the molecular mechanisms that govern the unique spatiotemporal aspects of non-canonical G protein activation by GIV and the relevance of this new paradigm in health and disease.
authors.affiliation: Department of Medicine, University of California at San Diego, La Jolla, CA, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Aznar
authors.affiliation: Department of Medicine, University of California at San Diego, La Jolla, CA, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Kalogriopoulos
authors.affiliation: Department of Medicine, University of California at San Diego, La Jolla, CA, USA.
authors.forename: Krishna K
authors.initials: KK
authors.lastname: Midde
authors.affiliation: Department of Medicine, University of California at San Diego, La Jolla, CA, USA.|Department of Cell and Molecular Medicine, University of California at San Diego, La Jolla, CA, USA.
authors.forename: Pradipta
authors.initials: P
authors.lastname: Ghosh
mesh_terms: D002318:Cardiovascular Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D002462:Cell Membrane / Q000378:metabolism; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D007425:Intracellular Membranes; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D025941:Protein Interaction Mapping; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*; D013997:Time Factors; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C502451:CCDC88A protein, human; D008840:Microfilament Proteins; D043562:Receptors, G-Protein-Coupled; D033921:Vesicular Transport Proteins
keywords: Golgi; autophagy; cdk5: Girdin; growth factor receptor tyrosine kinases; heterotrimeric G proteins