title: Tomosyn interacts with the SUMO E3 ligase PIASγ.
abstract: Protein modification by Small Ubiquitin-like MOdifier (SUMO) entities is involved in a number of neuronal functions, including synaptogenesis and synaptic plasticity. Tomosyn-1 (syntaxin-binding protein 5; STXPB5) binds to t-SNARE (Soluble NSF Attachment Protein Receptor) proteins to regulate neurotransmission and is one of the few neuronal SUMO substrate proteins identified. Here we used yeast two-hybrid screening to show that tomosyn-1 interacts with the SUMO E3 ligase PIASγ (Protein Inhibitor of Activated STAT; PIAS4 or ZMIZ6). This novel interaction involved the C-terminus of tomosyn-1 and the N-terminus of PIASγ. It was confirmed by two-way immunoprecipitation experiments using the full-length proteins expressed in HEK293T cells. Tomosyn-1 was preferentially modified by the SUMO-2/3 isoform. PIASγ-dependent modification of tomosyn-1 with SUMO-2/3 presents a novel mechanism to adapt secretory strength to the dynamic synaptic environment.
authors.affiliation: Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, Netherlands.
authors.forename: Cornelia J
authors.initials: CJ
authors.lastname: Geerts
authors.affiliation: Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, Netherlands.
authors.forename: Linda
authors.initials: L
authors.lastname: Jacobsen
authors.affiliation: Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, Netherlands.
authors.forename: Rhea
authors.initials: R
authors.lastname: van de Bospoort
authors.affiliation: Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, Netherlands; Department of Clinical Genetics, VU Medical Center, Amsterdam, Netherlands.
authors.forename: Matthijs
authors.initials: M
authors.lastname: Verhage
authors.affiliation: Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, Netherlands; Department of Clinical Genetics, VU Medical Center, Amsterdam, Netherlands.
authors.forename: Alexander J A
authors.initials: AJ
authors.lastname: Groffen
mesh_terms: D000818:Animals; D005033:Ethylmaleimide / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D000075223:Poly-ADP-Ribose Binding Proteins; D011485:Protein Binding / Q000187:drug effects; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism*; D050683:R-SNARE Proteins / Q000378:metabolism*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; C485891:PIAS4 protein, human; D000075223:Poly-ADP-Ribose Binding Proteins; D050828:Protein Inhibitors of Activated STAT; D050683:R-SNARE Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; C112618:tomosyn protein, mouse; D044767:Ubiquitin-Protein Ligases; D005033:Ethylmaleimide