Coronavirus M Protein Trafficking in Epithelial Cells Utilizes a Myosin Vb Splice Variant and Rab10
Category
Published on
Type
journal-article
Author
Lynne A. Lapierre and Joseph T. Roland and Elizabeth H. Manning and Catherine Caldwell and Honor L. Glenn and Pierre-Olivier Vidalain and Frederic Tangy and Brenda G. Hogue and C. A. M. de Haan and James R. Goldenring
Citation
Lapierre, L. A., Roland, J. T., Manning, E. H., Caldwell, C., Glenn, H. L., Vidalain, P.-O., Tangy, F., Hogue, B. G., de Haan, C. A. M., & Goldenring, J. R. (2024). Coronavirus M Protein Trafficking in Epithelial Cells Utilizes a Myosin Vb Splice Variant and Rab10. Cells, 13(2), 126. https://doi.org/10.3390/cells13020126
Abstract
The membrane (M) glycoprotein of coronaviruses (CoVs) serves as the nidus for virion assembly. Using a yeast two-hybrid screen, we identified the interaction of the cytosolic tail of Murine Hepatitis Virus (MHV-CoV) M protein with Myosin Vb (MYO5B), specifically with the alternative splice variant of cellular MYO5B including exon D (MYO5B+D), which mediates interaction with Rab10. When co-expressed in human lung epithelial A549 and canine kidney epithelial MDCK cells, MYO5B+D co-localized with the MHV-CoV M protein, as well as with the M proteins from Porcine Epidemic Diarrhea Virus (PEDV-CoV), Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome 2 (SARS-CoV-2). Co-expressed M proteins and MYO5B+D co-localized with endogenous Rab10 and Rab11a. We identified point mutations in MHV-CoV M that blocked the interaction with MYO5B+D in yeast 2-hybrid assays. One of these point mutations (E121K) was previously shown to block MHV-CoV virion assembly and its interaction with MYO5B+D. The E to K mutation at homologous positions in PEDV-CoV, MERS-CoV and SARS-CoV-2 M proteins also blocked colocalization with MYO5B+D. The knockdown of Rab10 blocked the co-localization of M proteins with MYO5B+D and was rescued by re-expression of CFP-Rab10. Our results suggest that CoV M proteins traffic through Rab10-containing systems, in association with MYO5B+D.
DOI
Funding
NSF-STC Biology with X-ray Lasers (NSF-1231306)
