Journal
JOURNAL OF NEUROCHEMISTRY
Volume 136, Issue 1, Pages 28-35Publisher
WILEY-BLACKWELL
DOI: 10.1111/jnc.13353
Keywords
Lzts2; ProSAPiP1; Shank3; Sipa1l1; Sipa1l2; Sipa1l3
Categories
Funding
- International Graduate School in Molecular Medicine of Ulm University
- Helmholtz Gesellschaft (RNA Dysmetabolism in ALS and FTD)
- Deutsche Forschungsgemeinschaft [DFG SBF1149]
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Rap GTPase-activating proteins (RapGAPs) are essential for synaptic function as they tightly regulate synaptic Rap signaling. Among the most abundant synaptic RapGAPs in brain are the Spine-associated RapGAPs (SPARs) Sipa1l1/SPAR and Sipa1l2/SPAR2, whereas nothing has been reported on Sipa1l3/SPAR3. In this study, we show that Sipa1l3/SPAR3 is conserved across species, has a distinct expression pattern in the developing rat brain and is localized at excitatory postsynapses. We further demonstrate that the Sipa1l3/SPAR3 C-terminus is required for postsynaptic targeting and represents an interaction module for Fezzins such as ProSAPiP1/Lzts3, a binding partner of the postsynaptic scaffold protein Shank3. Taken together, our data imply that Sipa1l3/SPAR3 is a hitherto unknown synaptic RapGAP, which is targeted to postsynaptic specializations and interacts with Fezzins.
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