TY - JOUR
T1 - Tumor suppressor down-regulated in renal cell carcinoma 1 (DRR1) is a stress-induced actin bundling factor that modulates synaptic efficacy and cognition
AU - Schmidt, Mathias V.
AU - Schülke, Jan Philip
AU - Liebl, Claudia
AU - Stiess, Michael
AU - Avrabos, Charilaos
AU - Bock, Jörg
AU - Wochnik, Gabriela M.
AU - Davies, Heather A.
AU - Zimmermann, Nicole
AU - Scharf, Sebastian H.
AU - Trümbach, Dietrich
AU - Wurst, Wolfgang
AU - Zieglgänsberger, Walter
AU - Turck, Christoph
AU - Holsboer, Florian
AU - Stewart, Michael G.
AU - Bradke, Frank
AU - Eder, Matthias
AU - Müller, Marianne B.
AU - Rein, Theo
PY - 2011/10/11
Y1 - 2011/10/11
N2 - 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 actindependent 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.
AB - 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 actindependent 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.
KW - Actin dynamics
KW - Stress physiology
KW - Stress regulation
KW - Synaptic plasticity
KW - TU3A
UR - http://www.scopus.com/inward/record.url?scp=80054758758&partnerID=8YFLogxK
U2 - 10.1073/pnas.1103318108
DO - 10.1073/pnas.1103318108
M3 - Article
C2 - 21969592
AN - SCOPUS:80054758758
SN - 0027-8424
VL - 108
SP - 17213
EP - 17218
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 41
ER -