Recruitment of Polarity Complexes and Tight Junction Proteins to the Site of Apical Bulk EndocytosisSummary
| Autor: | Anna E. Goldstein, Victoria G. Weis, Alexander W. Coutts, Milena Saqui-Salces, Evan S. Krystofiak, Anne R. Meyer, Amy C. Engevik, Tamene Melkamu, Izumi Kaji, James R. Goldenring |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
EPEC enteropathogenic Escherichia coli RC799-869 DMSO dimethyl sulfoxide Occludin Bulk endocytosis 0302 clinical medicine Rab Ras-related in brain Apical Bulk Endocytosis Myosin P-ERM phosphorylated ezrin–radixin–moesin ZO-1 Original Research Trafficking biology Tight junction Microvilli Chemistry Gastroenterology MYO5B myosin Vb Microvillus Inclusion Disease (MVID) Diseases of the digestive system. Gastroenterology Pals1 proteins associated with Lin-7 Endocytosis Cell biology medicine.anatomical_structure 030211 gastroenterology & hepatology Patj Pals1-associated tight junction protein Cortactin Intracellular ERM ezrin–radixin–moesin SEM scanning electron microscope PBS phosphate-buffered saline Myosin Vb Tight Junctions 03 medical and health sciences MVID microvillus inclusion disease medicine aPKC atypical protein kinase C KO knockout Tight Junction Proteins Hepatology Polarity Cdc42 cell division control protein 42 homolog Apical membrane Microvillus 030104 developmental biology Inclusions biology.protein |
| Zdroj: | Cellular and Molecular Gastroenterology and Hepatology, Vol 12, Iss 1, Pp 59-80 (2021) Cellular and Molecular Gastroenterology and Hepatology |
| Popis: | Background & Aims The molecular motor, Myosin Vb (MYO5B), is well documented for its role in trafficking cargo to the apical membrane of epithelial cells. Despite its involvement in regulating apical proteins, the role of MYO5B in cell polarity is less clear. Inactivating mutations in MYO5B result in microvillus inclusion disease (MVID), a disorder characterized by loss of key apical transporters and the presence of intracellular inclusions in enterocytes. We previously identified that inclusions in Myo5b knockout (KO) mice form from invagination of the apical brush border via apical bulk endocytosis. Herein, we sought to elucidate the role of polarity complexes and tight junction proteins during the formation of inclusions. Methods Intestinal tissue from neonatal control and Myo5b KO littermates was analyzed by immunofluorescence to determine the localization of polarity complexes and tight junction proteins. Results Proteins that make up the apical polarity complexes—Crumbs3 and Pars complexes—were associated with inclusions in Myo5b KO mice. In addition, tight junction proteins were observed to be concentrated over inclusions that were present at the apical membrane of Myo5b-deficient enterocytes in vivo and in vitro. Our mouse findings are complemented by immunostaining in a large animal swine model of MVID genetically engineered to express a human MVID-associated mutation that shows an accumulation of Claudin-2 over forming inclusions. The findings from our swine model of MVID suggest that a similar mechanism of tight junction accumulation occurs in patients with MVID. Conclusions These data show that apical bulk endocytosis involves the altered localization of apical polarity proteins and tight junction proteins after loss of Myo5b. Graphical abstract |
| Databáze: | OpenAIRE |
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