Sci. STKE, 6 January 2004
SYNAPSINS A Gap in Synapsin Function
Tu et al. discovered an unexpected role for synapsin Ia as an inhibitor of guanosine triphosphatase (GTPase)-activating proteins (GAPs) that stimulate Gz, a member of the Gi family of heterotrimeric guanine nucleotide-binding proteins found in neurons, platelets, and chromaffin cells. The synapsins are a family of synaptic phosphoproteins. Although their association with synaptic vesicles and the cytoskeleton has led to their implication in synaptic vesicle dynamics, other possible roles for these abundant proteins have remained undetermined. Observing that washing with high ionic strength buffer increased the Gz GAP activity of RGSZ1 in a membrane fraction from bovine brain, Tu et al. determined that a cytoskeletal or peripheral membrane protein was acting as a GAP inhibitor. After further purification, the authors isolated a high-molecular-weight GAP inhibitor that was identified as synapsin Ia by mass spectrometry, an identification confirmed by Western analysis. Recombinant rat synapsin Ia expressed in and then purified from Sf9 cells inhibited Gz GAP activity, whereas an antibody against synapsin depleted GAP-inhibitory activity from brain. Moreover, this GAP-inhibitory activity could not be isolated from the brains of mice lacking synapsin I and II. Although synapsin Ia inhibited the GAP activity of several RGS proteins, inhibition was selective for GAP activity directed at Gαz. The ability of synapsin Ia to inhibit GAP activity was attenuated by phosphorylation at Ser9 by either protein kinase A or p21-activated protein kinase. Thus, synapsin Ia appears to act as a selective Gz GAP inhibitor that is sensitive to regulation through at least two signaling pathways.
Y. Tu, S. K. Nayak, J. Woodson, E. M. Ross, Phosphorylation-regulated inhibition of the Gz GTPase-activating protein activity of RGS proteins by synapsin I. J. Biol. Chem. 278, 52273-52281 (2003). [Abstract] [Full Text]
Citation: A Gap in Synapsin Function. Sci. STKE 2004, tw3 (2004).
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