SH3BGRL3 binds to myosin 1c in a calcium dependent manner and modulates migration in the MDA-MB-231 cell line

Di Pisa, F, Pesenti, E, Bono, M, Mazzarello, AN, Bernardi, C, Lisanti, MP ORCID: https://orcid.org/0000-0003-2034-1382, Renzone, G, Scaloni, A, Ciccone, E, Fais, F, Bruno, S, Scartezzini, P and Ghiotto, F 2021, 'SH3BGRL3 binds to myosin 1c in a calcium dependent manner and modulates migration in the MDA-MB-231 cell line' , BMC Molecular and Cell Biology, 22 (1) , p. 41.

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Abstract

Background: The human SH3 domain Binding Glutamic acid Rich Like 3 (SH3BGRL3) gene is highly conserved in phylogeny and widely expressed in human tissues. However, its function is largely undetermined. The protein was found to be overexpressed in several tumors, and recent work suggested a possible relationship with EGFR family members. We aimed at further highlighting on these issues and investigated SH3BGRL3 molecular interactions and its role in cellular migration ability. Results: We first engineered the ErbB2-overexpressing SKBR3 cells to express exogenous SH3BGRL3, as well as wild type Myo1c or different deletion mutants. Confocal microscopy analysis indicated that SH3BGRL3 co-localized with Myo1c and ErbB2 at plasma membranes. However, co-immunoprecipitation assays and mass spectrometry demonstrated that SH3BGRL3 did not directly bind ErbB2, but specifically recognized Myo1c, on its IQ-bearing neck region. Importantly, the interaction with Myo1c was Ca2+-dependent. A role for SH3BGRL3 in cell migration was also assessed, as RNA interference of SH3BGRL3 in MDA-MB-231 cells, used as a classical migration model, remarkably impaired the migration ability of these cells. On the other side, its over-expression increased cell motility. Conclusion: The results of this study provide insights for the formulation of novel hypotheses on the putative role of SH3BGRL3 protein in the regulation of myosin-cytoskeleton dialog and in cell migration. It could be envisaged the SH3BGRL3-Myo1c interaction as a regulation mechanism for cytoskeleton dynamics. It is well known that, at low Ca2+ concentrations, the IQ domains of Myo1c are bound by calmodulin. Here we found that binding of Myo1c to SH3BGRL3 requires instead the presence of Ca2+. Thus, it could be hypothesized that Myo1c conformation may be modulated by Ca2+-driven mechanisms that involve alternative binding by calmodulin or SH3BGRL3, for the regulation of cytoskeletal activity.

Item Type:	Article
Additional Information:	** From Springer Nature via Jisc Publications Router ** Licence for this article: http://creativecommons.org/licenses/by/4.0/ **Journal IDs: eissn 2661-8850 **Article IDs: publisher-id: s12860-021-00379-1; manuscript: 379 **History: collection 12-2021; online 11-08-2021; published 11-08-2021; registration 04-08-2021; accepted 26-07-2021; submitted 20-01-2021
Schools:	Schools > School of Environment and Life Sciences > Biomedical Research Centre
Journal or Publication Title:	BMC Molecular and Cell Biology
Publisher:	BioMed Central
ISSN:	2661-8850
Related URLs:	Publication
Funders:	Fondazione Maria Piaggio Casarsa, Genova, Italy, Associazione Italiana Ricerca sul Cancro (AIRC), Italian Ministry of Health, Campania Bioscience
SWORD Depositor:	Publications Router
Depositing User:	Publications Router
Date Deposited:	12 Aug 2021 09:24
Last Modified:	16 Feb 2022 07:31
URI:	https://usir.salford.ac.uk/id/eprint/61488

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