title: A vesicle trafficking protein αSNAP regulates Paneth cell differentiation in vivo.
abstract: A soluble N-ethylmaleimide-sensitive factor-attachment protein alpha (αSNAP) is a multifunctional scaffolding protein that regulates intracellular vesicle trafficking and signaling. In cultured intestinal epithelial cells, αSNAP has been shown to be essential for cell survival, motility, and adhesion; however, its physiologic functions in the intestinal mucosa remain unknown. In the present study, we used a mouse with a spontaneous hydrocephalus with hop gait (hyh) mutation of αSNAP to examine the roles of this trafficking protein in regulating intestinal epithelial homeostasis in vivo. Homozygous hyh mice demonstrated decreased expression of αSNAP protein in the intestinal epithelium, but did not display gross abnormalities of epithelial architecture in the colon and ileum. Such αSNAP depletion attenuated differentiation of small intestinal epithelial enteroids ex vivo. Furthermore, αSNAP-deficient mutant animals displayed reduced formation of lysozyme granules in small intestinal crypts and decreased expression of lysozyme and defensins in the intestinal mucosa, which is indicative of defects in Paneth cell differentiation. By contrast, development of Goblet cells, enteroendocrine cells, and assembly of enterocyte apical junctions was not altered in hyh mutant mice. Our data revealed a novel role of αSNAP in the intestinal Paneth cell differentiation in vivo.
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Susana
authors.initials: S
authors.lastname: Lechuga
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Nayden G
authors.initials: NG
authors.lastname: Naydenov
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Feygin
authors.affiliation: Department of Cell Biology, Genetics, and Physiology, University of Malaga, Malaga, Spain.
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Jimenez
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23298, USA; VCU Institute of Molecular Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA. Electronic address: Andrei.Ivanov@vcuhealth.org.
authors.forename: Andrei I
authors.initials: AI
authors.lastname: Ivanov
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D008297:Male; D051379:Mice; D019879:Paneth Cells / Q000166:cytology* / Q000378:metabolism*; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins / Q000378:metabolism*
chemical_list: D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins
keywords: Adherens junctions; Intestinal mucosa; Membrane fusion; NAPA; Tight junctions