Return of the GDI: the GoLoco motif in cell division.
The GoLoco motif is a 19-amino-acid sequence with guanine nucleotide dissociation inhibitor activity against G-alpha subunits of the adenylyl-cyclase-inhibitory subclass. The GoLoco motif is present as an independent element within multidomain signaling regulators, such as Loco, RGS12, RGS14, and Rap1GAP, as well as in tandem arrays in proteins, such as AGS3, G18, LGN, Pcp-2/L7, and Partner of Inscuteable (Pins/Rapsynoid). Here we discuss the biochemical mechanisms of GoLoco motif action on G-alpha subunits in light of the recent crystal structure of G-alpha-i1 bound to the RGS14 GoLoco motif. Currently, there is sparse evidence for GoLoco motif regulation of canonical G-protein-coupled receptor signaling. Rather, studies of asymmetric cell division in Drosophila and Caenorhabditis elegans, as well as mammalian mitosis, implicate GoLoco proteins, such as Pins, GPR-1/GPR-2, LGN, and RGS14, in mitotic spindle organization and force generation. We discuss potential mechanisms by which GoLoco/Galpha complexes might modulate spindle dynamics.
Willard
Francis S
FS
Department of Pharmacology, Lineberger Comprehensive Cancer Center, and UNC Neuroscience Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599-7365, USA. fwillard@med.unc.edu
Kimple
Randall J
RJ
Siderovski
David P
DP
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division / Q000502:physiology*; D017124:Conserved Sequence; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010766:Phosphorylation; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D020730:Guanine Nucleotide Dissociation Inhibitors; D043562:Receptors, G-Protein-Coupled