Myosin Vb and rab11a regulate ezrin phosphorylation in enterocytes
Microvilli at the apical surface of enterocytes allow the efficient absorption of nutrients in the intestine. Ezrin activation by its phosphorylation at T567 is important for microvilli development, but how ezrin phosphorylation is controlled is not well understood. We demonstrate that a subset of k...
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Veröffentlicht in: | Journal of cell science 2014-01 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Microvilli at the apical surface of enterocytes allow the efficient absorption of nutrients in the intestine. Ezrin activation by its phosphorylation at T567 is important for microvilli development, but how ezrin phosphorylation is controlled is not well understood. We demonstrate that a subset of kinases that phosphorylate ezrin closely co-distributes with apical recycling endosome marker rab11a in the subapical domain. Expression of dominant-negative rab11a mutant or depletion of the rab11a-binding motor protein myosin Vb prevents the subapical enrichment of rab11a and these kinases and inhibits ezrin phosphorylation and microvilli development, without affecting the polarized distribution of ezrin itself. We observe a similar loss of the subapical enrichment of rab11a and the kinases and reduced phosphorylation of ezrin in Microvillus inclusion disease, which is associated with MYO5B mutations, intestinal microvilli atrophy and mal-absorption. Thus, part of the machinery for ezrin activation depends on myosin Vb/rab11a-controlled recycling endosomes which, we propose, may act as subapical signaling platforms that enterocytes use to regulate microvilli development and maintain human intestinal function. |
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ISSN: | 0021-9533 1477-9137 |
DOI: | 10.1242/jcs.137273 |