Tomosyn interacts with the SUMO E3 ligase PIASγ

Cornelia J Geerts; Linda Jacobsen; Rhea van de Bospoort; Matthijs Verhage; Alexander J A Groffen

doi:10.1371/journal.pone.0091697

Tomosyn interacts with the SUMO E3 ligase PIASγ

PLoS One. 2014 Mar 10;9(3):e91697. doi: 10.1371/journal.pone.0091697. eCollection 2014.

Authors

Cornelia J Geerts¹, Linda Jacobsen¹, Rhea van de Bospoort¹, Matthijs Verhage², Alexander J A Groffen²

Affiliations

¹ Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, Netherlands.
² 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.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Ethylmaleimide / pharmacology
HEK293 Cells
Humans
Male
Mice, Inbred BALB C
Nerve Tissue Proteins / metabolism*
Poly-ADP-Ribose Binding Proteins
Protein Binding / drug effects
Protein Inhibitors of Activated STAT / metabolism*
R-SNARE Proteins / metabolism*
Small Ubiquitin-Related Modifier Proteins / metabolism*
Two-Hybrid System Techniques
Ubiquitin-Protein Ligases / metabolism*

Substances

Nerve Tissue Proteins
PIAS4 protein, human
Poly-ADP-Ribose Binding Proteins
Protein Inhibitors of Activated STAT
R-SNARE Proteins
Small Ubiquitin-Related Modifier Proteins
tomosyn protein, mouse
Ubiquitin-Protein Ligases
Ethylmaleimide

Grants and funding

This study was supported by the Centre for Medical Systems Biology [CMSB2 project 3.3.5; http://www.cmsb.nl/research/]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.