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

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 me...

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Bibliographic Details
Published in:International journal of molecular sciences 2018-12, Vol.19 (12), p.3993
Main Authors: Kretzschmar, Anja, Schülke, Jan-Philip, Masana, Mercè, Dürre, Katharina, Müller, Marianne B, Bausch, Andreas R, Rein, Theo
Format: Article
Language:English
Subjects:
Actin
actin dynamics
Amino acids
Binding sites
Bundling
Cell spreading
Cognition
Confocal microscopy
Cytoskeleton
DRR1
Elongation
FAM107A
Fluorescence
Fluorescence recovery after photobleaching
Gene expression
Kidney cancer
Mental disorders
Molecular modelling
Motility
Nucleation
Photobleaching
Physiology
Polymerization
Profilin
Proteins
Renal cell carcinoma
Sedimentation & deposition
Serum response factor
stress physiology
TU3A
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Summary: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. 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. 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. DRR1 impacts actin dynamics in several ways with implications for cytoskeletal dynamics in stress physiology and pathophysiology.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms19123993