Actin is a key protein of the muscle contraction system. It is present in the cytoplasm, providing motor and framework function through polymerization into F-actin, as well as in the nuclei of all non-muscle cells, where most actin is present in a globular form and participates in processes related to the cell’s genetic apparatus, including transcription and DNA repair. Actin interacts with a large number of proteins that form a whole class of actin-binding proteins. Since the functional role of nuclear actin differs significantly from the role of actin in the cell cytoplasm, the goal of this study was to compare the interactome of cytoplasmic and nuclear actin.
Using the BioGRID and StringDB databases, proteins that interact with actin experimentally confirmed were selected. Four groups of actin-binding proteins were identified depending on their cellular localization: only cytoplasm, only nucleus, and nucleus and cytoplasm, and others. The analysis of biological processes in the interactome showed that nuclear proteins participate in most key nuclear processes, from DNA damage response to transcription regulation, while cytoplasmic actin-binding proteins are involved in the formation, regulation, and functioning of the cytoskeleton. The analysis of the structure of actin-binding proteins showed a large proportion of internally disordered proteins, most of which are part of membraneless organelles (MLOs). It is known that proteins prone to liquid–liquid phase separation (LLPS) play a key role in the formation of MLOs. Interestingly, although significantly more nuclear proteins are prone to LLPS than cytoplasmic proteins (44% vs. 25%), the drivers of the formation of MLOs in the cytoplasm are significantly (four times) more than in the nucleus. From the pool of actin-binding proteins, 28 clusters were identified, within each of which proteins are capable of forming physical contacts with each other.
Author Contributions
Y.I.M.: Data curation, Formal analysis, Investigation, Method-ology, Validation, Visualization, Writing—original draft, Writing—review & editing. O.I.P.: Data curation, Formal analysis, Investigation, Methodology, Writing—review & editing. I.A.A.: Data curation, Formal analysis, Investigation, Methodology, Writing—review & editing. I.M.K.: Data curation, Formal analysis, Investigation, Validation, Writing—review & editing. K.K.T.: Data curation, Formal analysis, Investigation, Writing—review & editing, Supervision, Validation. A.V.F.: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Method-ology, Supervision, Validation, Visualization, Writing—original draft, Writing—review & editing. All authors have read and agreed to the published version of the manuscript.
Funding
The work was supported by the Russian Science Foundation (project No. 23-15-00494, IMK).
Institutional Review Board Statement
Not applicable.
Informed Consent Statement
Not applicable.
Data Availability Statement
A list of actin-binding proteins examined in the study is available here: https://thebiogrid.org/106575/summary/homo-sapiens/actb.html (accessed on 1 April 2024).
Conflicts of Interest
The authors declare no conflicts of interest.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 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 (https://creativecommons.org/licenses/by/4.0/).