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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Authors | Mathias V Schmidt, Jan-Philip Schülke, Claudia Liebl, Michael Stiess, Charilaos Avrabos, Jörg Bock, Gabriela M Wochnik, Heather A Davies, Nicole Zimmermann, Sebastian H Scharf, Dietrich Trümbach, Wolfgang Wurst, Walter Zieglgänsberger, Christoph Turck, Florian Holsboer, Michael G Stewart, Frank Bradke, Matthias Eder, Marianne B Müller, Theo Rein |
Journal | Proceedings of the National Academy of Sciences of the United States of America
(Proc Natl Acad Sci U S A)
Vol. 108
Issue 41
Pg. 17213-8
(Oct 11 2011)
ISSN: 1091-6490 [Electronic] United States |
PMID | 21969592
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Actins
- DRR1 protein, mouse
- Tumor Suppressor Proteins
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Topics |
- Actins
(metabolism)
- Animals
- Behavior, Animal
(physiology)
- Brain
(cytology, physiology)
- Cognition
(physiology)
- Genes, Tumor Suppressor
- HEK293 Cells
- Humans
- Male
- Maze Learning
(physiology)
- Mice
- Mice, Inbred C57BL
- Mice, Transgenic
- Neurites
(metabolism, ultrastructure)
- Protein Binding
- Stress, Physiological
- Synapses
(physiology)
- Tumor Suppressor Proteins
(genetics, physiology)
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