Rab22a regulates the establishment of epithelial polarity

Rab22a regulates the establishment of epithelial polarity

Membrane trafficking establishes and maintains epithelial polarity. Rab22a has a polarized distribution in activated T-cells, but its role in epithelial polarity has not been investigated. We showed previously that Rab14 acts upstream of Arf6 to establish the apical membrane initiation site (AMIS),...

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Bibliographic Details
Published in:Small GTPases Vol. 12; no. 4; pp. 282 - 293
Main Authors: Blum, Isabella R., Behling-Hess, Caroline, Padilla-Rodriguez, Marco, Momtaz, Samina, Cox, Christopher, Wilson, Jean M.
Format: Journal Article
Language:English
Published: United States Taylor & Francis 04-07-2021
Subjects:
ADP-Ribosylation Factor 6 - genetics
ADP-Ribosylation Factor 6 - metabolism
Animals
apical membrane initiation site
Arf6
Cell Membrane - metabolism
Cell Polarity
Dogs
Efa6
Endocytosis
Endosomes - metabolism
Epithelial Cells - cytology
Epithelial Cells - physiology
Guanine Nucleotide Exchange Factors - genetics
Guanine Nucleotide Exchange Factors - metabolism
HEK293 Cells
Humans
Madin Darby Canine Kidney Cells
membrane trafficking
multi-lumen
polarity
Protein Transport
rab GTP-Binding Proteins - genetics
rab GTP-Binding Proteins - metabolism
Rab14
Rab22a
Research Paper
multi-lumen
apical membrane initiation site
Efa6
Rab14
Arf6
membrane trafficking
Rab22a
polarity
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Summary:Membrane trafficking establishes and maintains epithelial polarity. Rab22a has a polarized distribution in activated T-cells, but its role in epithelial polarity has not been investigated. We showed previously that Rab14 acts upstream of Arf6 to establish the apical membrane initiation site (AMIS), but its interaction with Rab22a is unknown. Here we show that Rab14 and Rab22a colocalize in endosomes of both unpolarized and polarized MDCK cells and Rab22a localizes to the cell:cell interface of polarizing cell pairs. Knockdown of Rab22a results in a multi-lumen phenotype in three-dimensional culture. Further, overexpression of Rab22a in Rab14 knockdown cells rescues the multi-lumen phenotype observed with Rab14 knockdown, suggesting that Rab22a is downstream of Rab14. Because of the relationship between Rab14 and Arf6, we investigated the effect of Rab22a knockdown on Arf6. We find that Rab22a knockdown results in decreased active Arf6 and that Rab22a co-immunoprecipitates with the Arf6 GEF EFA6. In addition, EFA6 is retained in intracellular puncta in Rab22a KD cells. These results suggest that Rab22a acts downstream of Rab14 to traffic EFA6 to the AMIS to regulate Arf6 in the establishment of polarity.
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ISSN:2154-1248
2154-1256
DOI:10.1080/21541248.2020.1754104