دورية أكاديمية
Myosin 5b is required for proper localization of the intermicrovillar adhesion complex in the intestinal brush border.
| العنوان: | Myosin 5b is required for proper localization of the intermicrovillar adhesion complex in the intestinal brush border. |
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| المؤلفون: | Dooley SA; Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, South Carolina., Engevik KA; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas., Digrazia J; Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, South Carolina., Stubler R; Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, South Carolina., Kaji I; Section of Surgical Sciences, Vanderbilt University Medical Center, Nashville, Tennessee.; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, Tennessee., Krystofiak E; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee.; Cell Imaging Shared Resource, Vanderbilt University, Nashville, Tennessee., Engevik AC; Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, South Carolina. |
| المصدر: | American journal of physiology. Gastrointestinal and liver physiology [Am J Physiol Gastrointest Liver Physiol] 2022 Nov 01; Vol. 323 (5), pp. G501-G510. Date of Electronic Publication: 2022 Oct 11. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901227 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1547 (Electronic) Linking ISSN: 01931857 NLM ISO Abbreviation: Am J Physiol Gastrointest Liver Physiol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Bethesda, MD : American Physiological Society |
| مواضيع طبية MeSH: | Enterocytes*/metabolism , Microvilli*/metabolism , Myosin Type V*/genetics , Myosin Type V*/metabolism, Animals ; Mice ; Cell Cycle Proteins/metabolism ; Cytoskeletal Proteins/metabolism ; Intestinal Mucosa/metabolism ; Intestines ; Myosin Heavy Chains/genetics ; Myosin Heavy Chains/metabolism |
| مستخلص: | Intestinal enterocytes have an elaborate apical membrane of actin-rich protrusions known as microvilli. The organization of microvilli is orchestrated by the intermicrovillar adhesion complex (IMAC), which connects the distal tips of adjacent microvilli. The IMAC is composed of CDHR2 and CDHR5 as well as the scaffolding proteins USH1C, ANKS4B, and Myosin 7b (MYO7B). To create an IMAC, cells must transport the proteins to the apical membrane. Myosin 5b (MYO5B) is a molecular motor that traffics ion transporters to the apical membrane of enterocytes, and we hypothesized that MYO5B may also be responsible for the localization of IMAC proteins. To address this question, we used two different mouse models: 1 ) neonatal germline MYO5B knockout (MYO5B KO) mice and 2 ) adult intestinal-specific tamoxifen-inducible VillinCre ERT2 ;MYO5B flox/flox mice. In control mice, immunostaining revealed that CDHR2, CDHR5, USH1C, and MYO7B were highly enriched at the tips of the microvilli. In contrast, neonatal germline and adult MYO5B-deficient mice showed loss of apical CDHR2, CDHR5, and MYO7B in the brush border and accumulation in a subapical compartment. Colocalization analysis revealed decreased Mander's coefficients in adult inducible MYO5B-deficient mice compared with control mice for CDHR2, CDHR5, USH1C, and MYO7B. Scanning electron microscopy images further demonstrated aberrant microvilli packing in adult inducible MYO5B-deficient mouse small intestine. These data indicate that MYO5B is responsible for the delivery of IMAC components to the apical membrane. NEW & NOTEWORTHY The intestinal epithelium absorbs nutrients and water through an elaborate apical membrane of highly organized microvilli. Microvilli organization is regulated by the intermicrovillar adhesion complexes, which create links between neighboring microvilli and control microvilli packing and density. In this study, we report a new trafficking partner of the IMAC, Myosin 5b. Loss of Myosin 5b results in a disorganized brush border and failure of IMAC proteins to reach the distal tips of microvilli. |
| References: | Dev Cell. 2016 Jan 25;36(2):179-89. (PMID: 26812017) Mol Biol Cell. 2005 May;16(5):2443-57. (PMID: 15758024) Gastroenterology. 2020 Jun;158(8):2236-2249.e9. (PMID: 32112796) Proc Natl Acad Sci U S A. 2015 Oct 6;112(40):12408-13. (PMID: 26392529) Curr Opin Cell Biol. 2022 Aug;77:102117. (PMID: 35870341) J Cell Biol. 1986 Nov;103(5):1979-90. (PMID: 3023393) Nat Genet. 2008 Oct;40(10):1163-5. (PMID: 18724368) Gut. 1988 Nov;29(11):1557-63. (PMID: 3209113) JCI Insight. 2021 Aug 23;6(16):. (PMID: 34197342) Anat Rec. 1985 Dec;213(4):520-8. (PMID: 4083533) Hum Mutat. 2010 May;31(5):544-51. (PMID: 20186687) J Cell Biol. 1987 Aug;105(2):691-703. (PMID: 3305521) Nature. 2007 Sep 6;449(7158):87-91. (PMID: 17805295) J Cell Biol. 2019 Nov 4;218(11):3647-3662. (PMID: 31562230) J Biol Chem. 2020 Jul 10;295(28):9281-9296. (PMID: 32209652) J Cell Biol. 1974 Sep;62(3):679-94. (PMID: 4854072) Cell Mol Gastroenterol Hepatol. 2021;12(1):59-80. (PMID: 33548596) Cell Mol Gastroenterol Hepatol. 2016 Feb 1;2(2):131-157. (PMID: 27019864) Sci Rep. 2015 Jul 23;5:12312. (PMID: 26201991) Dev Cell. 2016 Jan 25;36(2):190-200. (PMID: 26812018) J Cell Biol. 1984 Sep;99(3):909-17. (PMID: 6470044) Gastroenterology. 2018 Sep;155(3):815-828. (PMID: 29782846) Nat Rev Mater. 2021;6(5):402-420. (PMID: 33623712) Curr Biol. 2021 May 24;31(10):R586-R602. (PMID: 34033792) J Cell Biol. 2014 Nov 24;207(4):441-51. (PMID: 25422372) Cell. 2014 Apr 10;157(2):433-446. (PMID: 24725409) Gastroenterology. 1978 Nov;75(5):783-90. (PMID: 100367) Cell Mol Gastroenterol Hepatol. 2016 Jan 1;2(1):48-62.e3. (PMID: 26855967) PLoS One. 2016 Oct 13;11(10):e0164775. (PMID: 27736989) Nat Genet. 2000 Sep;26(1):56-60. (PMID: 10973248) Curr Biol. 2016 Oct 24;26(20):2717-2728. (PMID: 27666969) Nat Commun. 2016 Mar 01;7:10833. (PMID: 26926603) Nat Methods. 2012 Jul;9(7):671-5. (PMID: 22930834) Gastroenterology. 2018 Dec;155(6):1883-1897.e10. (PMID: 30144427) Trends Genet. 2022 Jul;38(7):724-751. (PMID: 35367088) Gastroenterology. 2020 Oct;159(4):1390-1405.e20. (PMID: 32534933) |
| معلومات مُعتمدة: | P30 DK123704 United States DK NIDDK NIH HHS; K01 DK121869 United States DK NIDDK NIH HHS; P20 GM130457 United States GM NIGMS NIH HHS; F32 DK130288 United States DK NIDDK NIH HHS; R01 DK128190 United States DK NIDDK NIH HHS |
| فهرسة مساهمة: | Keywords: enterocyte; intermicrovillar adhesion complex (IMAC); intestine; microvilli; myosin |
| المشرفين على المادة: | 0 (Cell Cycle Proteins) 0 (Cytoskeletal Proteins) 0 (Myo5B protein, mouse) EC 3.6.4.1 (Myosin Heavy Chains) EC 3.6.1.- (Myosin Type V) 0 (Ush1c protein, mouse) |
| تواريخ الأحداث: | Date Created: 20221011 Date Completed: 20221103 Latest Revision: 20231213 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC9639760 |
| DOI: | 10.1152/ajpgi.00212.2022 |
| PMID: | 36218265 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1522-1547 |
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| DOI: | 10.1152/ajpgi.00212.2022 |