title: Both the anti- and pro-apoptotic functions of villin regulate cell turnover and intestinal homeostasis.
abstract: In the small intestine, epithelial cells are derived from stem cells in the crypts, migrate up the villus as they differentiate and are ultimately shed from the villus tips. This process of proliferation and shedding is tightly regulated to maintain the intestinal architecture and tissue homeostasis. Apoptosis regulates both the number of stem cells in the crypts as well as the sloughing of cells from the villus tips. Previously, we have shown that villin, an epithelial cell-specific actin-binding protein functions as an anti-apoptotic protein in the gastrointestinal epithelium. The expression of villin is highest in the apoptosis-resistant villus cells and lowest in the apoptosis-sensitive crypts. In this study we report that villin is cleaved in the intestinal mucosa to generate a pro-apoptotic fragment that is spatially restricted to the villus tips. This cleaved villin fragment severs actin in an unregulated fashion to initiate the extrusion and subsequent apoptosis of effete cells from the villus tips. Using villin knockout mice, we validate the physiological role of villin in apoptosis and cell extrusion from the gastrointestinal epithelium. Our study also highlights the potential role of villin's pro-apoptotic function in the pathogenesis of inflammatory bowel disease, ischemia-reperfusion injury, enteroinvasive bacterial and parasitic infections.
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: Yaohong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston TX 77204, USA.
authors.forename: Sudeep P
authors.initials: SP
authors.lastname: George
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston TX 77204, USA.
authors.forename: Swati
authors.initials: S
authors.lastname: Roy
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston TX 77204, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Pham
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston TX 77204, USA.
authors.forename: Amin
authors.initials: A
authors.lastname: Esmaeilniakooshkghazi
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston TX 77204, USA.|Baylor College of Medicine, Houston TX 77030, USA.
authors.forename: Seema
authors.initials: S
authors.lastname: Khurana
mesh_terms: D000818:Animals; D017209:Apoptosis; D002465:Cell Movement; D004285:Dogs; D004848:Epithelium / Q000378:metabolism; D006706:Homeostasis; D007422:Intestines / Q000166:cytology* / Q000648:ultrastructure; D061985:Madin Darby Canine Kidney Cells; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000378:metabolism*; D008954:Models, Biological
chemical_list: D008840:Microfilament Proteins; C026615:villin