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SPAR2, a novel SPAR‐related protein with GAP activity for Rap1 and Rap2
Author(s) -
Spilker Christina,
Acuña Sanhueza Gustavo A.,
Böckers Tobias M.,
Kreutz Michael R.,
Gundelfinger Eckart D.
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04991.x
Subject(s) - microbiology and biotechnology , hippocampal formation , cerebellum , dendritic spine , synaptic plasticity , biology , scaffold protein , pdz domain , gtpase , chemistry , neuroscience , biochemistry , signal transduction , receptor
Spine‐associated RapGAP 2 (SPAR2) is a novel GTPase activating protein (GAP) for the small GTPase Rap that shows significant sequence homology to SPAR, a synaptic RapGAP that was reported to regulate spine morphology in hippocampal neurons. SPAR2, like SPAR, interacts with the recently described synaptic scaffolding protein ProSAP‐interacting protein (ProSAPiP), which in turn binds to the PDZ domain of ProSAP/Shank post‐synaptic density proteins. In subcellular fractionation experiments, SPAR2 is enriched in synaptosomes and post‐synaptic density fractions indicating that it is a synaptic protein. Furthermore, we could show using in vitro GAP assays that SPAR2 has GAP activity for Rap1 and Rap2. Expression in COS‐7 cells, however, revealed different actin‐binding properties of SPAR2 and SPAR. Additionally, over‐expression of SPAR2 in cultured hippocampal neurons did not affect spine morphology as it was reported for SPAR. In situ hybridization studies also revealed a differential tissue distribution of SPAR and SPAR2 with SPAR2 transcripts being mainly expressed in cerebellar and hippocampal granule cells. Moreover, in the cerebellum SPAR2 is developmentally regulated with a peak of expression around the period of synapse formation. Our results imply that SPAR2 is a new RapGAP with specific functions in cerebellar and hippocampal granule cells.