MARK2/EMK1/Par-1Balpha Phosphorylation of Rab11-family Interacting Protein 2 is Necessary for the Timely Establishment of Polarity in Madin-Darby Canine Kidney Cells
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Molecular Biology
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Rab11a, myosin Vb, and the Rab11-family interacting protein 2 (FIP2) regulate plasma membrane recycling in epithelial cells. This study sought to characterize more fully Rab11-FIP2 function by identifying kinase activities modifying Rab11-FIP2. We have found that gastric microsomal membrane extracts phosphorylate Rab11-FIP2 on serine 227. We identified the kinase that phosphorylated Rab11-FIP2 as MARK2/EMK1/Par-1Balpha (MARK2), and recombinant MARK2 phosphorylated Rab11-FIP2 only on serine 227. We created stable Madin-Darby canine kidney (MDCK) cell lines expressing enhanced green fluorescent protein-Rab11-FIP2 wild type or a nonphosphorylatable mutant [Rab11-FIP2(S227A)]. Analysis of these cell lines demonstrates a new role for Rab11-FIP2 in addition to that in the plasma membrane recycling system. In calcium switch assays, cells expressing Rab11-FIP2(S227A) showed a defect in the timely reestablishment of p120-containing junctional complexes. However, Rab11-FIP2(S227A) did not affect localization with recycling system components or the normal function of apical recycling and transcytosis pathways. These results indicate that phosphorylation of Rab11-FIP2 on serine 227 by MARK2 regulates an alternative pathway modulating the establishment of epithelial polarity.
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Rathan-Kumar S, Roland J, Momoh M, Goldstein A, Lapierre L, Manning E Am J Physiol Gastrointest Liver Physiol. 2022; 323(3):G239-G254.
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King L, Zhang H, Gould C, Thomas D, Whitehead L, Simpson K PLoS One. 2020; 15(10):e0240746.
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Datta A, Yang C, Limbutara K, Chou C, Rinschen M, Raghuram V FASEB J. 2020; 34(5):6129-6146.
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Mooney M, Ryabinin P, Wilmot B, Bhatt P, Mill J, Nigg J Transl Psychiatry. 2020; 10(1):8.
PMID: 32066674 PMC: 7026179. DOI: 10.1038/s41398-020-0710-4.