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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.

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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.

Item Type: Journal Article
Copyright Holders: 2011 M. V. Schmidt
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/Department: Science
Science > Life, Health and Chemical Sciences
Interdisciplinary Research Centre: Biomedical Research Network (BRN)
Item ID: 29707
Depositing User: Michael Stewart
Date Deposited: 07 Oct 2011 08:24
Last Modified: 20 Mar 2015 11:53
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