Kretzschmar, AnjaSchülke, Jan-PhilipMasana Nadal, MercèDürre, KatharinaMüller, Marianne B.Bausch, Andreas R.Rein, Theo2020-04-202020-04-202018-12-111661-6596https://hdl.handle.net/2445/156118Cytoskeletal 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.30 p.application/pdfengcc-by (c) Kretzschmar, Anja et al., 2018http://creativecommons.org/licenses/by/3.0/esCitosqueletProteïnes citosquelètiquesCytoskeletonCytoskeletal proteinsinfo:eu-repo/semantics/article6835392020-04-20info:eu-repo/semantics/openAccess30545002