Coronavirus M Protein Trafficking in Epithelial Cells Utilizes a Myosin Vb Splice Variant and Rab10.

Coronavirus M Protein Trafficking in Epithelial Cells Utilizes a Myosin Vb Splice Variant and Rab10.

Publication date: Jan 10, 2024

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.

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Concepts Keywords
Coronaviruses Animals
E121k coronavirus
Kidney Coronavirus M Proteins
Traffic Coronavirus M Proteins
Yeast Dogs
M protein
membrane recycling
Myosin Vb
rab GTP-Binding Proteins
rab GTP-Binding Proteins
Rab10 protein, human
Rab10 protein, mouse
Saccharomyces cerevisiae
Viral Matrix Proteins
Viral Matrix Proteins


Type Source Name
disease VO M protein
disease VO Glycoprotein
drug DRUGBANK L-Aspartic Acid
disease MESH Middle East Respiratory Syndrome
disease MESH Severe Acute Respiratory Syndrome
disease MESH point mutations
disease VO USA
disease MESH Infections
disease VO vaccination
disease MESH Infectious Diseases
pathway REACTOME Developmental Biology
disease VO Viruses
disease MESH COVID 19
drug DRUGBANK Coenzyme M
drug DRUGBANK L-Asparagine
drug DRUGBANK Serine
drug DRUGBANK L-Threonine
drug DRUGBANK Trestolone
disease IDO host
drug DRUGBANK Tretamine
drug DRUGBANK Amino acids
disease IDO assay
drug DRUGBANK L-Alanine
disease VO organ
drug DRUGBANK L-Lysine
drug DRUGBANK Albendazole
drug DRUGBANK Doxycycline
disease VO Respiratory syncytial virus
disease MESH influenza
disease IDO site
disease VO protocol
disease MESH hepatitis
drug DRUGBANK Histidine
drug DRUGBANK Tromethamine
drug DRUGBANK Edetic Acid
drug DRUGBANK Polyethylene glycol
drug DRUGBANK Dimethyl sulfoxide
drug DRUGBANK L-Tryptophan
drug DRUGBANK L-Leucine
disease IDO colony
drug DRUGBANK Nitrogen
drug DRUGBANK Potassium Chloride
drug DRUGBANK Magnesium sulfate
disease VO volume
drug DRUGBANK Chloramphenicol
drug DRUGBANK Water
drug DRUGBANK Medical air
drug DRUGBANK Tetracycline
disease VO Env
drug DRUGBANK Puromycin
drug DRUGBANK Sodium lauryl sulfate
drug DRUGBANK Gold
disease VO ANOVA
drug DRUGBANK (S)-Des-Me-Ampa
disease IDO cell
pathway KEGG Drug metabolism

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