The stress-inducible protein DRR1 exerts distinct effects on actin dynamics

Anja Kretzschmar, Jan Philip Schülke, Mercè Masana, Katharina Dürre, Marianne B. Müller, Andreas R. Bausch, Theo Rein

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

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 Factin 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.

Original languageEnglish
Article number3993
JournalInternational Journal of Molecular Sciences
Volume19
Issue number12
DOIs
StatePublished - Dec 2018

Keywords

  • Actin dynamics
  • Cytoskeleton
  • DRR1
  • FAM107A
  • Stress physiology
  • TU3A

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