title: JMY is involved in anterograde vesicle trafficking from the trans-Golgi network.
abstract: Junction-mediating and regulatory protein (JMY) was originally identified as a transcriptional co-factor in the p53-response to DNA damage. Aside from this nuclear function, recent years have uncovered an additional function of JMY, namely in cytoskeleton remodelling and actin assembly. The C-terminus of JMY comprises a canonical VCA-module, the sequence signature of Arp2/3 complex activators. Furthermore, tandem repeats of 3 WH2 (V, or more recently also W) domains render JMY capable of Arp2/3 independent actin assembly. The motility promoting cytoplasmic function of JMY is abrogated upon DNA-damage and nuclear translocation of JMY. To address the precise cellular function of JMY in cellular actin rearrangements, we have searched for potential new interaction partners by mass spectrometry. We identified several candidates and correlated their localization with the subcellular dynamics of JMY. JMY is localized to dynamic vesiculo-tubular structures throughout the cytoplasm, which are decorated with actin and Arp2/3 complex. Moreover, JMY partially colocalizes and interacts with VAP-A, which is involved in vesicle-based transport processes. Finally, overexpression of JMY results in Golgi dispersal by loss from the trans-site and affects VSV-G transport. These analyses, together with biochemical experiments, indicate that JMY drives vesicular trafficking in the trans-Golgi region and at ER-membrane contact sites (MCS), distinct from other Arp2/3 activators involved in vesicle transport processes such as the related WHAMM or WASH.
authors.affiliation: Institute for Molecular Cell Biology, University of Münster, Schlossplatz 5, 48149 Münster, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Schlüter
authors.affiliation: Experimental Tumorbiology, University of Münster, Badestrasse 9, 48149 Münster, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Waschbüsch
authors.affiliation: Institute for Molecular Cell Biology, University of Münster, Schlossplatz 5, 48149 Münster, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Anft
authors.affiliation: Institute for Molecular Cell Biology, University of Münster, Schlossplatz 5, 48149 Münster, Germany.
authors.forename: Debbie
authors.initials: D
authors.lastname: Hügging
authors.affiliation: Institute for Molecular Cell Biology, University of Münster, Schlossplatz 5, 48149 Münster, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Kind
authors.affiliation: Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Hänisch
authors.affiliation: Laboratoire d'Enzymologie et Biochimie Structurales, CNRS UPR3082, Avenue de la Terrasse, 91190 Gif-sur-Yvette, France.
authors.forename: Goran
authors.initials: G
authors.lastname: Lakisic
authors.affiliation: Laboratoire d'Enzymologie et Biochimie Structurales, CNRS UPR3082, Avenue de la Terrasse, 91190 Gif-sur-Yvette, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Gautreau
authors.affiliation: Experimental Tumorbiology, University of Münster, Badestrasse 9, 48149 Münster, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Barnekow
authors.affiliation: Institute for Molecular Cell Biology, University of Münster, Schlossplatz 5, 48149 Münster, Germany; Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany. Electronic address: theresia.stradal@helmholtz-hzi.de.
authors.forename: Theresia E B
authors.initials: TE
authors.lastname: Stradal
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins; D002522:Chlorocebus aethiops; D006367:HeLa Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D055503:Protein Multimerization; D021381:Protein Transport; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D033921:Vesicular Transport Proteins; D014759:Viral Envelope Proteins / Q000378:metabolism; D021601:trans-Golgi Network / Q000378:metabolism*
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C028391:G protein, vesicular stomatitis virus; C485677:Jmy protein, mouse; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; C491920:Vapa protein, mouse; D033921:Vesicular Transport Proteins; D014759:Viral Envelope Proteins
keywords: Actin dynamics; Arp2/3 complex; Golgi; JMY; NPF; Nucleation promoting factors; Tubular vesicles; Vesicle traffic; WHAMM