Tumor suppressor down-regulated in renal cell carcinoma 1 (DRR1) is a stress-induced actin bundling factor that modulates synaptic efficacy and cognition

Schmidt, Mathias V.; Schülke, Jan-Philip; Liebl, Claudia; Stiess, Michael; Avrabos, Charilaos; Bock, Jörg; Wochnik, Gabriela M.; Davies, Heather A.; Zimmermann, Nicole; Scharf, Sebastian H.; Trümbach, Dietrich; Wurst, Wolfgang; Zieglgänsberger, Walter; Turck, Christoph; Holsboer, Florian; Stewart, Michael G.; Bradke, Frank; Eder, Matthias; Müller, Marianne B. and Rein, Theo (2011). Tumor suppressor down-regulated in renal cell carcinoma 1 (DRR1) is a stress-induced actin bundling factor that modulates synaptic efficacy and cognition. Proceedings of the National Academy of Sciences of the United States of America, 108(41) pp. 17213–17218.

DOI: https://doi.org/10.1073/pnas.1103318108

Abstract

Stress has been identified as a major causal factor for many mental disorders. However, our knowledge about the chain of molecular and cellular events translating stress experience into altered behavior is still rather scant. Here, we have characterized a murine ortholog of the putative tumor suppressor gene DRR1 as a unique stress-induced protein in brain. It binds to actin, promotes bundling and stabilization of actin filaments, and impacts on actin-dependent neurite outgrowth. Endogenous DRR1 localizes to some, but not all, synapses, with preference for the presynaptic region. Hippocampal virus-mediated enhancement of DRR1 expression reduced spine density, diminished the probability of synaptic glutamate release, and altered cognitive performance. DRR1 emerges as a protein to link stress with actin dynamics, which in addition is able to act on synaptic function and cognition.

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About

• Item ORO ID
• 29707
• Item Type
• Journal Item
• ISSN
• 1091-6490
• Project Funding Details

• Funded Project Name	Project ID	Funding Body
  Not Set	Not Set	Klinische Kooperationsgruppe, Max Planck InInstitute
  Not Set	Not Set	Helmholtz Zentrum Muenchen
  BMBF-NGFN Framework	NGFN01GS08151	German Federal Ministry of Education and Research
  BMBF-NGFN Framework	DIGTOP-01GS0858	German Federal Ministry of Education and Research
  Not Set	Not Set	Helmholtz Society Helmholtz Alliance for Mental Health in an Ageing Society)
  EU FP7 Memstick	201600	European Union

• Keywords
• actin dynamics; stress physiology; stress regulation; synaptic plasticity; TU3A
• Academic Unit or School
• Faculty of Science, Technology, Engineering and Mathematics (STEM)
  Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
• Copyright Holders
• © 2011 M. V. Schmidt
• Depositing User
• Michael Stewart