title: Myosin Vb and Rab11a regulate phosphorylation of ezrin in enterocytes.
abstract: 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 such 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 malabsorption. Thus, part of the machinery for ezrin activation depends on recycling endosomes controlled by myosin Vb and Rab11a which, we propose, might act as subapical signaling platforms that enterocytes use to regulate development of microvilli and maintain human intestinal function.
authors.affiliation: Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Herschel S
authors.initials: HS
authors.lastname: Dhekne
authors.forename: Nai-Hua
authors.initials: NH
authors.lastname: Hsiao
authors.forename: Pieter
authors.initials: P
authors.lastname: Roelofs
authors.forename: Meena
authors.initials: M
authors.lastname: Kumari
authors.forename: Christiaan L
authors.initials: CL
authors.lastname: Slim
authors.forename: Edmond H H M
authors.initials: EH
authors.lastname: Rings
authors.forename: Sven C D
authors.initials: SC
authors.lastname: van Ijzendoorn
mesh_terms: D045744:Cell Line, Tumor; D016764:Cell Polarity; D018389:Codon, Nonsense; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism; D020895:Enterocytes / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008286:Malabsorption Syndromes / Q000235:genetics; D008871:Microvilli / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009081:Mucolipidoses / Q000235:genetics; D018995:Myosin Heavy Chains / Q000502:physiology*; D024701:Myosin Type V / Q000502:physiology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021381:Protein Transport; D020691:rab GTP-Binding Proteins / Q000502:physiology*; D000099149:Ezrin; D000099293:Protein Kinase C-lambda; D000099193:rab11 GTP-Binding Proteins; D000099317:Hippo Kinases
chemical_list: D018389:Codon, Nonsense; D003598:Cytoskeletal Proteins; D007527:Isoenzymes; D018995:Myosin Heavy Chains; D024701:Myosin Type V; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases; D020691:rab GTP-Binding Proteins; D000099149:Ezrin; D000099293:Protein Kinase C-lambda; D000099193:rab11 GTP-Binding Proteins; C505832:MYO5B protein, human; C430908:STK26 protein, human; D000099317:Hippo Kinases
keywords: Apical; Enterocyte; Microvilli; Microvillus inclusion disease; Recycling endosome