Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Kretzschmar, Anja, Schülke, Jan-Philip, Masana, Mercè, Dürre, Katharina, Müller, Marianne B., Bausch, Andreas R., Rein, Theo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321462/
https://www.ncbi.nlm.nih.gov/pubmed/30545002
http://dx.doi.org/10.3390/ijms19123993
_version_ 1783385448299626496
author Kretzschmar, Anja
Schülke, Jan-Philip
Masana, Mercè
Dürre, Katharina
Müller, Marianne B.
Bausch, Andreas R.
Rein, Theo
author_facet Kretzschmar, Anja
Schülke, Jan-Philip
Masana, Mercè
Dürre, Katharina
Müller, Marianne B.
Bausch, Andreas R.
Rein, Theo
author_sort Kretzschmar, Anja
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6321462
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-63214622019-01-07 The Stress-Inducible Protein DRR1 Exerts Distinct Effects on Actin Dynamics Kretzschmar, Anja Schülke, Jan-Philip Masana, Mercè Dürre, Katharina Müller, Marianne B. Bausch, Andreas R. Rein, Theo Int J Mol Sci Article 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. MDPI 2018-12-11 /pmc/articles/PMC6321462/ /pubmed/30545002 http://dx.doi.org/10.3390/ijms19123993 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kretzschmar, Anja
Schülke, Jan-Philip
Masana, Mercè
Dürre, Katharina
Müller, Marianne B.
Bausch, Andreas R.
Rein, Theo
The Stress-Inducible Protein DRR1 Exerts Distinct Effects on Actin Dynamics
title The Stress-Inducible Protein DRR1 Exerts Distinct Effects on Actin Dynamics
title_full The Stress-Inducible Protein DRR1 Exerts Distinct Effects on Actin Dynamics
title_fullStr The Stress-Inducible Protein DRR1 Exerts Distinct Effects on Actin Dynamics
title_full_unstemmed The Stress-Inducible Protein DRR1 Exerts Distinct Effects on Actin Dynamics
title_short The Stress-Inducible Protein DRR1 Exerts Distinct Effects on Actin Dynamics
title_sort stress-inducible protein drr1 exerts distinct effects on actin dynamics
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321462/
https://www.ncbi.nlm.nih.gov/pubmed/30545002
http://dx.doi.org/10.3390/ijms19123993
work_keys_str_mv AT kretzschmaranja thestressinducibleproteindrr1exertsdistincteffectsonactindynamics
AT schulkejanphilip thestressinducibleproteindrr1exertsdistincteffectsonactindynamics
AT masanamerce thestressinducibleproteindrr1exertsdistincteffectsonactindynamics
AT durrekatharina thestressinducibleproteindrr1exertsdistincteffectsonactindynamics
AT mullermarianneb thestressinducibleproteindrr1exertsdistincteffectsonactindynamics
AT bauschandreasr thestressinducibleproteindrr1exertsdistincteffectsonactindynamics
AT reintheo thestressinducibleproteindrr1exertsdistincteffectsonactindynamics
AT kretzschmaranja stressinducibleproteindrr1exertsdistincteffectsonactindynamics
AT schulkejanphilip stressinducibleproteindrr1exertsdistincteffectsonactindynamics
AT masanamerce stressinducibleproteindrr1exertsdistincteffectsonactindynamics
AT durrekatharina stressinducibleproteindrr1exertsdistincteffectsonactindynamics
AT mullermarianneb stressinducibleproteindrr1exertsdistincteffectsonactindynamics
AT bauschandreasr stressinducibleproteindrr1exertsdistincteffectsonactindynamics
AT reintheo stressinducibleproteindrr1exertsdistincteffectsonactindynamics