Yip1 Domain Family, Member 6 (Yipf6) Mutation Induces Spontaneous Intestinal Inflammation in Mice

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2012 Jul 18

PMID 22802641

Citations 22

Authors

Katharina Brandl

Wataru Tomisato

Xiaohong Li

Christina Neppl

Elaine Pirie

Werner Falk

Yu Xia

Eva Marie Y Moresco

Roberto Baccala

Argyrios N Theofilopoulos

Bernd Schnabl

Bruce Beutler

Affiliations

Soon will be listed here.

Abstract

Using an environmentally sensitized genetic screen we identified mutations that cause inflammatory colitis in mice. The X-linked Klein-Zschocher (KLZ) mutation created a null allele of Yipf6, a member of a gene family believed to regulate vesicular transport in yeast, but without known functions in mammals. Yipf6 is a five transmembrane-spanning protein associated with Golgi compartments. Klein-Zschocher mutants were extremely sensitive to colitis induced by dextran sodium sulfate (DSS) and developed spontaneous ileitis and colitis after 16 mo of age in specific pathogen-free housing conditions. Electron microscopy, gene expression, and immunocytochemistry analyses provided evidence that impaired intestinal homeostasis stemmed from defective formation and secretion of large secretory granules from Paneth and goblet cells. These studies support a tissue- and organ-specific function for Yipf6 in the maintenance of intestinal homeostasis and implicate the orthologous human gene as a disease susceptibility locus.

Citing Articles

Trans-Golgi protein TVP23B regulates host-microbe interactions via Paneth cell homeostasis and Goblet cell glycosylation.

Song R, McAlpine W, Fond A, Nair-Gill E, Choi J, Nystrom E Nat Commun. 2023; 14(1):3652.

PMID: 37339972 PMC: 10282085. DOI: 10.1038/s41467-023-39398-1.

Microarray Analysis Reveals Changes in tRNA-Derived Small RNAs (tsRNAs) Expression in Mice with Septic Cardiomyopathy.

Yuan L, Tang Y, Yin L, Lin X, Luo Z, Wang S Genes (Basel). 2022; 13(12).

PMID: 36553526 PMC: 9778384. DOI: 10.3390/genes13122258.

Exploring the eukaryotic Yip and REEP/Yop superfamily of membrane-shaping adapter proteins (MSAPs): A cacophony or harmony of structure and function?.

Angelotti T Front Mol Biosci. 2022; 9:912848.

PMID: 36060263 PMC: 9437294. DOI: 10.3389/fmolb.2022.912848.

A mutation phenocopies oblique alleles altered vesicle trafficking.

Kandasamy S, Couto K, Thackeray J PeerJ. 2021; 9:e12175.

PMID: 34721959 PMC: 8520396. DOI: 10.7717/peerj.12175.

Towards complete and error-free genome assemblies of all vertebrate species.

Rhie A, McCarthy S, Fedrigo O, Damas J, Formenti G, Koren S Nature. 2021; 592(7856):737-746.

PMID: 33911273 PMC: 8081667. DOI: 10.1038/s41586-021-03451-0.

References

Brandl K, Plitas G, Mihu C, Ubeda C, Jia T, Fleisher M . Vancomycin-resistant enterococci exploit antibiotic-induced innate immune deficits. Nature. 2008; 455(7214):804-7. PMC: 2663337. DOI: 10.1038/nature07250. View

Cadwell K, Liu J, Brown S, Miyoshi H, Loh J, Lennerz J . A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells. Nature. 2008; 456(7219):259-63. PMC: 2695978. DOI: 10.1038/nature07416. View

Sansonetti P . War and peace at mucosal surfaces. Nat Rev Immunol. 2004; 4(12):953-64. DOI: 10.1038/nri1499. View

Shakoori A, Fujii G, Yoshimura S, Kitamura M, Nakayama K, Ito T . Identification of a five-pass transmembrane protein family localizing in the Golgi apparatus and the ER. Biochem Biophys Res Commun. 2003; 312(3):850-7. DOI: 10.1016/j.bbrc.2003.10.197. View

Heazlewood C, Cook M, Eri R, Price G, Tauro S, Taupin D . Aberrant mucin assembly in mice causes endoplasmic reticulum stress and spontaneous inflammation resembling ulcerative colitis. PLoS Med. 2008; 5(3):e54. PMC: 2270292. DOI: 10.1371/journal.pmed.0050054. View

Takeda K, Clausen B, Kaisho T, Tsujimura T, Terada N, Forster I . Enhanced Th1 activity and development of chronic enterocolitis in mice devoid of Stat3 in macrophages and neutrophils. Immunity. 1999; 10(1):39-49. DOI: 10.1016/s1074-7613(00)80005-9. View

Brandl K, Tomisato W, Beutler B . Inflammatory bowel disease and ADAM17 deletion. N Engl J Med. 2012; 366(2):190. DOI: 10.1056/NEJMc1113859. View

Tang B, Ong Y, Huang B, Wei S, Wong E, Qi R . A membrane protein enriched in endoplasmic reticulum exit sites interacts with COPII. J Biol Chem. 2001; 276(43):40008-17. DOI: 10.1074/jbc.M106189200. View

Hammer R, Maika S, Richardson J, Tang J, Taurog J . Spontaneous inflammatory disease in transgenic rats expressing HLA-B27 and human beta 2m: an animal model of HLA-B27-associated human disorders. Cell. 1990; 63(5):1099-112. DOI: 10.1016/0092-8674(90)90512-d. View

10.

Brandl K, Rutschmann S, Li X, Du X, Xiao N, Schnabl B . Enhanced sensitivity to DSS colitis caused by a hypomorphic Mbtps1 mutation disrupting the ATF6-driven unfolded protein response. Proc Natl Acad Sci U S A. 2009; 106(9):3300-5. PMC: 2651297. DOI: 10.1073/pnas.0813036106. View

11.

Blaydon D, Biancheri P, Di W, Plagnol V, Cabral R, Brooke M . Inflammatory skin and bowel disease linked to ADAM17 deletion. N Engl J Med. 2011; 365(16):1502-8. DOI: 10.1056/NEJMoa1100721. View

12.

Yang X, Matern H, Gallwitz D . Specific binding to a novel and essential Golgi membrane protein (Yip1p) functionally links the transport GTPases Ypt1p and Ypt31p. EMBO J. 1998; 17(17):4954-63. PMC: 1170824. DOI: 10.1093/emboj/17.17.4954. View

13.

Brandl K, Sun L, Neppl C, Siggs O, Le Gall S, Tomisato W . MyD88 signaling in nonhematopoietic cells protects mice against induced colitis by regulating specific EGF receptor ligands. Proc Natl Acad Sci U S A. 2010; 107(46):19967-72. PMC: 2993336. DOI: 10.1073/pnas.1014669107. View

14.

Kuhn R, Lohler J, Rennick D, Rajewsky K, Muller W . Interleukin-10-deficient mice develop chronic enterocolitis. Cell. 1993; 75(2):263-74. DOI: 10.1016/0092-8674(93)80068-p. View

15.

Kaser A, Lee A, Franke A, Glickman J, Zeissig S, Tilg H . XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease. Cell. 2008; 134(5):743-56. PMC: 2586148. DOI: 10.1016/j.cell.2008.07.021. View

16.

Welte T, Zhang S, Wang T, Zhang Z, Hesslein D, Yin Z . STAT3 deletion during hematopoiesis causes Crohn's disease-like pathogenesis and lethality: a critical role of STAT3 in innate immunity. Proc Natl Acad Sci U S A. 2003; 100(4):1879-84. PMC: 149927. DOI: 10.1073/pnas.0237137100. View

17.

Brandl K, Plitas G, Schnabl B, DeMatteo R, Pamer E . MyD88-mediated signals induce the bactericidal lectin RegIII gamma and protect mice against intestinal Listeria monocytogenes infection. J Exp Med. 2007; 204(8):1891-900. PMC: 2118673. DOI: 10.1084/jem.20070563. View

18.

Esworthy R, Aranda R, Martin M, Doroshow J, Binder S, Chu F . Mice with combined disruption of Gpx1 and Gpx2 genes have colitis. Am J Physiol Gastrointest Liver Physiol. 2001; 281(3):G848-55. DOI: 10.1152/ajpgi.2001.281.3.G848. View

19.

Calero M, Winand N, Collins R . Identification of the novel proteins Yip4p and Yip5p as Rab GTPase interacting factors. FEBS Lett. 2002; 515(1-3):89-98. DOI: 10.1016/s0014-5793(02)02442-0. View

20.

Thiagarajah J, Zhao D, Verkman A . Impaired enterocyte proliferation in aquaporin-3 deficiency in mouse models of colitis. Gut. 2007; 56(11):1529-35. PMC: 2095633. DOI: 10.1136/gut.2006.104620. View