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Schmidt, M.V.* ; Schülke, .J.-P.* ; Liebl, C.* ; Stiess, M.* ; Avrabos, C.* ; Bock, J.* ; Wochnik, GM.* ; Davies, H.A.* ; Zimmermann, N.* ; Scharf, S.H.* ; Trümbach, D. ; Wurst, W. ; Zieglgänsberger, W.* ; Turck, C.* ; Holsboer, F.* ; Stewart, M.G.* ; Bradke, F.* ; Eder, M.* ; Müller, M.B.* ; Rein, T.

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

Proc. Natl. Acad. Sci. U.S.A. 108, 17213-17218 (2011)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords actin dynamics; stress physiology; stress regulation; synaptic plasticity; TU3A
Language english
Publication Year 2011
HGF-reported in Year 2011
ISSN (print) / ISBN 0027-8424
e-ISSN 1091-6490
Journal Proceedings of the National Academy of Sciences of the United States of America
Quellenangaben Volume: 108, Issue: 41, Pages: 17213-17218 Article Number: , Supplement: ,
Publisher National Academy of Sciences
Publishing Place Washington, DC, USA
Reviewing status Peer reviewed
Institute(s) Institute of Developmental Genetics (IDG)
POF-Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30204 - Cell Programming and Repair
Research field(s) Genetics and Epidemiology
PSP Element(s) G-520600-001
G-500500-001
PubMed ID 21969592
DOI 10.1073/pnas.1103318108
Scopus ID 80054758758
Erfassungsdatum 2011-11-08
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