Morphoregulatory Functions of the RNA-Binding Motif Protein 3 in Cell Spreading, Polarity and Migration

Authors

J. Pilotte, The Scripps Research Institute
W. Kiosses, The Scripps Research Institute
S. W. Chan, The Scripps Research Institute
H. P. Makarenkova, The Scripps Research Institute
Esther E. Dupont-Versteegden, University of KentuckyFollow
P. W. Vanderklish, The Scripps Research Institute

Abstract

RNA-binding proteins are emerging as key regulators of transitions in cell morphology. The RNA-binding motif protein 3 (RBM3) is a cold-inducible RNA-binding protein with broadly relevant roles in cellular protection, and putative functions in cancer and development. Several findings suggest that RBM3 has morphoregulatory functions germane to its roles in these contexts. For example, RBM3 helps maintain the morphological integrity of cell protrusions during cell stress and disease. Moreover, it is highly expressed in migrating neurons of the developing brain and in cancer invadopodia, suggesting roles in migration. We here show that RBM3 regulates cell polarity, spreading and migration. RBM3 was present in spreading initiation centers, filopodia and blebs that formed during cell spreading in cell lines and primary myoblasts. Reducing RBM3 triggered exaggerated spreading, increased RhoA expression, and a loss of polarity that was rescued by Rho kinase inhibition and overexpression of CRMP2. High RBM3 expression enhanced the motility of cells migrating by a mesenchymal mode involving extension of long protrusions, whereas RBM3 knockdown slowed migration, greatly reducing the ability of cells to extend protrusions and impairing multiple processes that require directional migration. These data establish novel functions of RBM3 of potential significance to tissue repair, metastasis and development.

Document Type

Article

Publication Date

5-9-2018

Notes/Citation Information

Published in Scientific Reports, v. 8, article no. 7367, p. 1-19.

© The Author(s) 2018

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Digital Object Identifier (DOI)

https://doi.org/10.1038/s41598-018-25668-2

Funding Information

This work was funded in part by NIH National Institute of Neurological Disorders and Stroke grant 5R01NS066053 to PWV, and NIH National Eye Institute grant 1R01EY026202 to HPM.

Related Content

Supplementary information accompanies this paper at https://doi.org/10.1038/s41598-018-25668-2.

Repository Citation

Pilotte, J.; Kiosses, W.; Chan, S. W.; Makarenkova, H. P.; Dupont-Versteegden, Esther E.; and Vanderklish, P. W., "Morphoregulatory Functions of the RNA-Binding Motif Protein 3 in Cell Spreading, Polarity and Migration" (2018). Physical Therapy Faculty Publications. 93.
https://uknowledge.uky.edu/rehabsci_facpub/93