title: Sipa1l3/SPAR3 is targeted to postsynaptic specializations and interacts with the Fezzin ProSAPiP1/Lzts3.
abstract: 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. Spine-associated RapGAPs (SPARs) are essential modulators of synaptic signaling. Our study is the first to characterize the SPAR family member Sipa1l3/SPAR3 in neuronal tissue. We show that Sipa1l3/SPAR3 is conserved across species, has a distinct expression pattern in brain and is localized to excitatory postsynapses via its C-terminus, which represents an interaction module for other postsynaptic proteins including the Fezzin ProSAPiP1/Lzts3.
authors.affiliation: Institute for Anatomy and Cell Biology, Ulm University, Ulm, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Dolnik
authors.affiliation: Institute for Anatomy and Cell Biology, Ulm University, Ulm, Germany.|International Graduate School in Molecular Medicine Ulm, IGradU, Ulm University, Ulm, Germany.
authors.forename: Noreen
authors.initials: N
authors.lastname: Kanwal
authors.affiliation: Institute for Anatomy and Cell Biology, Ulm University, Ulm, Germany.|International Graduate School in Molecular Medicine Ulm, IGradU, Ulm University, Ulm, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Mackert
authors.affiliation: Institute for Anatomy and Cell Biology, Ulm University, Ulm, Germany.|International Graduate School in Molecular Medicine Ulm, IGradU, Ulm University, Ulm, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Halbedl
authors.affiliation: Institute for Anatomy and Cell Biology, Ulm University, Ulm, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Proepper
authors.affiliation: Institute for Anatomy and Cell Biology, Ulm University, Ulm, Germany.
authors.forename: Juergen
authors.initials: J
authors.lastname: Bockmann
authors.affiliation: Institute for Anatomy and Cell Biology, Ulm University, Ulm, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schoen
authors.affiliation: Institute for Anatomy and Cell Biology, Ulm University, Ulm, Germany.
authors.forename: Tobias M
authors.initials: TM
authors.lastname: Boeckers
authors.affiliation: Institute for Biochemistry and Molecular Biology, Ulm University, Ulm, Germany.
authors.forename: Susanne J
authors.initials: SJ
authors.lastname: Kühl
authors.affiliation: Institute for Anatomy and Cell Biology, Ulm University, Ulm, Germany.|Department of Neurology, Ulm University, Ulm, Germany.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Schmeisser
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D019556:COS Cells; D002352:Carrier Proteins / Q000096:biosynthesis*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004285:Dogs; D005260:Female; D020690:GTPase-Activating Proteins / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D051379:Mice; D002679:Pan troglodytes; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013569:Synapses / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*
chemical_list: D002352:Carrier Proteins; D020690:GTPase-Activating Proteins; C503711:LZTS3 protein, human; C523118:Lzts3 protein, rat; D008565:Membrane Proteins; C533460:SIPA1L1 protein, human; D025521:Tumor Suppressor Proteins
keywords: Lzts2; ProSAPiP1; Shank3; Sipa1l1; Sipa1l2; Sipa1l3