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Free keywords:
LONG-TERM POTENTIATION; DYNAMICS; BRAIN; DEPRESSION; FILAMENTS;
BEHAVIOR; DISEASE; MEMORY; MODEL; MICEMultidisciplinary Sciences; actin dynamics; stress physiology; stress regulation; synaptic
plasticity; TU3A;
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.
