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Open AccessArticle

The Stress-Inducible Protein DRR1 Exerts Distinct Effects on Actin Dynamics

1
Max Planck Institute of Psychiatry, Kraepelinstraße 2-10, 80805 München, Germany
2
Department of Psychiatry and Psychotherapy & Focus Program Translational Neuroscience, Johannes Gutenberg Universität Medical Center, 55131 Mainz, Germany
3
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, IDIBAPS, CIBERNED, Casanova, 143, 08036 Barcelona, Spain
4
Lehrstuhl für Biophysik E27, Technische Universität München, 85748 Garching, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(12), 3993; https://doi.org/10.3390/ijms19123993
Received: 29 October 2018 / Revised: 7 December 2018 / Accepted: 10 December 2018 / Published: 11 December 2018
(This article belongs to the Special Issue Molecular Psychiatry)
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. View Full-Text
Keywords: stress physiology; cytoskeleton; actin dynamics; DRR1; TU3A; FAM107A stress physiology; cytoskeleton; actin dynamics; DRR1; TU3A; FAM107A
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MDPI and ACS Style

Kretzschmar, A.; Schülke, J.-P.; Masana, M.; Dürre, K.; Müller, M.B.; Bausch, A.R.; Rein, T. The Stress-Inducible Protein DRR1 Exerts Distinct Effects on Actin Dynamics. Int. J. Mol. Sci. 2018, 19, 3993.

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