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.

Viewing alternatives

Metrics

Public Attention

Altmetrics from Altmetric

Number of Citations

Citations from Dimensions

Item Actions

Export

About

  • Item ORO ID
  • 29707
  • Item Type
  • Journal Item
  • ISSN
  • 1091-6490
  • Project Funding Details
  • Funded Project NameProject IDFunding Body
    Not SetNot SetKlinische Kooperationsgruppe, Max Planck InInstitute
    Not SetNot SetHelmholtz Zentrum Muenchen
    BMBF-NGFN FrameworkNGFN01GS08151German Federal Ministry of Education and Research
    BMBF-NGFN FrameworkDIGTOP-01GS0858German Federal Ministry of Education and Research
    Not SetNot SetHelmholtz Society Helmholtz Alliance for Mental Health in an Ageing Society)
    EU FP7 Memstick201600European 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

Recommendations