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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/156118
The stress-inducible protein DRR1 exerts distinct effects on actin dynamics
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Cytoskeletal dynamics are pivotal to memory, learning, and stress physiology, and thus psychiatric diseases. Downregulated in renal cell carcinoma 1 (DRR1) protein was characterized as the link between stress, actin dynamics, neuronal function, and cognition. To elucidate the underlying molecular mechanisms, we undertook a domain analysis of DRR1 and probed the effects on actin binding, polymerization, and bundling, as well as on actin-dependent cellular processes. METHODS: DRR1 domains were cloned and expressed as recombinant proteins to perform in vitro analysis of actin dynamics (binding, bundling, polymerization, and nucleation). Cellular actin-dependent processes were analyzed in transfected HeLa cells with fluorescence recovery after photobleaching (FRAP) and confocal microscopy. RESULTS: DRR1 features an actin binding site at each terminus, separated by a coiled coil domain. DRR1 enhances actin bundling, the cellular F-actin content, and serum response factor (SRF)-dependent transcription, while it diminishes actin filament elongation, cell spreading, and actin treadmilling. We also provide evidence for a nucleation effect of DRR1. Blocking of pointed end elongation by addition of profilin indicates DRR1 as a novel barbed end capping factor. CONCLUSIONS: DRR1 impacts actin dynamics in several ways with implications for cytoskeletal dynamics in stress physiology and pathophysiology.
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KRETZSCHMAR, Anja, SCHÜLKE, Jan-philip, MASANA NADAL, Mercè, DÜRRE, Katharina, MÜLLER, Marianne b., BAUSCH, Andreas r., REIN, Theo. The stress-inducible protein DRR1 exerts distinct effects on actin dynamics. _International Journal of Molecular Sciences_. 2018. Vol. 19, núm. 12, pàgs. 3993. [consulta: 21 de gener de 2026]. ISSN: 1661-6596. [Disponible a: https://hdl.handle.net/2445/156118]