title: Tumor suppressor down-regulated in renal cell carcinoma 1 (DRR1) is a stress-induced actin bundling factor that modulates synaptic efficacy and cognition.
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.
authors.affiliation: Max Planck Institute of Psychiatry, 80804 Munich,  Germany.
authors.forename: Mathias V
authors.initials: MV
authors.lastname: Schmidt
authors.forename: Jan-Philip
authors.initials: JP
authors.lastname: Schülke
authors.forename: Claudia
authors.initials: C
authors.lastname: Liebl
authors.forename: Michael
authors.initials: M
authors.lastname: Stiess
authors.forename: Charilaos
authors.initials: C
authors.lastname: Avrabos
authors.forename: Jörg
authors.initials: J
authors.lastname: Bock
authors.forename: Gabriela M
authors.initials: GM
authors.lastname: Wochnik
authors.forename: Heather A
authors.initials: HA
authors.lastname: Davies
authors.forename: Nicole
authors.initials: N
authors.lastname: Zimmermann
authors.forename: Sebastian H
authors.initials: SH
authors.lastname: Scharf
authors.forename: Dietrich
authors.initials: D
authors.lastname: Trümbach
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wurst
authors.forename: Walter
authors.initials: W
authors.lastname: Zieglgänsberger
authors.forename: Christoph
authors.initials: C
authors.lastname: Turck
authors.forename: Florian
authors.initials: F
authors.lastname: Holsboer
authors.forename: Michael G
authors.initials: MG
authors.lastname: Stewart
authors.forename: Frank
authors.initials: F
authors.lastname: Bradke
authors.forename: Matthias
authors.initials: M
authors.lastname: Eder
authors.forename: Marianne B
authors.initials: MB
authors.lastname: Müller
authors.forename: Theo
authors.initials: T
authors.lastname: Rein
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000502:physiology; D003071:Cognition / Q000502:physiology*; D016147:Genes, Tumor Suppressor; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016501:Neurites / Q000378:metabolism / Q000648:ultrastructure; D011485:Protein Binding; D013312:Stress, Physiological; D013569:Synapses / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D000199:Actins; C549076:DRR1 protein, mouse; D025521:Tumor Suppressor Proteins