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
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.
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.
||2011 M. V. Schmidt
|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)|
|Not Set||EU FP7 Memstick||European Union|
||actin dynamics; stress physiology; stress regulation; synaptic plasticity; TU3A
Science > Life, Health and Chemical Sciences
|Interdisciplinary Research Centre:
||Biomedical Research Network (BRN)
||07 Oct 2011 08:24
||07 Mar 2014 15:05
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