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Intestinal epithelial tight junction barrier regulation by autophagy-related protein ATG6/beclin 1.
Wong, Morgan; Ganapathy, Ashwinkumar Subramenium; Suchanec, Eric; Laidler, Laura; Ma, Thomas; Nighot, Prashant.
Afiliación
  • Wong M; Department of Internal Medicine, University of New Mexico School of Medicine , Albuquerque, New Mexico.
  • Ganapathy AS; Department of Medicine, College of Medicine, Pennsylvania State University , Hershey, Pennsylvania.
  • Suchanec E; Department of Medicine, College of Medicine, Pennsylvania State University , Hershey, Pennsylvania.
  • Laidler L; Department of Internal Medicine, University of New Mexico School of Medicine , Albuquerque, New Mexico.
  • Ma T; Department of Medicine, College of Medicine, Pennsylvania State University , Hershey, Pennsylvania.
  • Nighot P; Department of Medicine, College of Medicine, Pennsylvania State University , Hershey, Pennsylvania.
Am J Physiol Cell Physiol ; 316(5): C753-C765, 2019 05 01.
Article en En | MEDLINE | ID: mdl-30892937
A defective tight junction (TJ) barrier is a key pathogenic factor for inflammatory bowel disease. Previously, we have shown that autophagy, a cell survival mechanism, enhances intestinal epithelial TJ barrier function. Autophagy-related protein-6 (ATG6/beclin 1), a key protein in the autophagy pathway, also plays a role in the endocytic pathway. The constitutive role of beclin 1 in the intestinal TJ barrier is not known. In Caco-2 cells, beclin 1 was found to be coimmunoprecipitated with the TJ protein occludin and colocalized with occludin on the membrane. Treatment of Caco-2 cells with beclin 1 peptide [transactivating regulatory protein (Tat)-beclin 1] reduced TJ barrier function. Activation of beclin 1 increased occludin endocytosis and reduced total occludin protein level. In contrast, beclin 1 siRNA transfection enhanced Caco-2 TJ barrier function. In pharmacologic and genetic autophagy inhibition studies, the constitutive function of beclin 1 in the TJ barrier was found to be autophagy independent. However, de novo induction of autophagy with starvation or rapamycin prevented Tat-beclin 1-induced increase in TJ permeability and reduction in occludin level. Induction of autophagy also resulted in reduced beclin 1-occludin association. In mouse colon, beclin 1 colocalized with occludin on the epithelial membrane. Perfusion of mouse colon with beclin 1 peptide caused an increase in colonic TJ permeability that was prevented by in vivo induction of autophagy. These findings show that beclin 1 plays a constitutive, autophagy-independent role in the regulation of intestinal TJ barrier function via endocytosis of occludin. Autophagy terminates constitutive beclin 1 function in the TJ barrier and enhances the TJ barrier.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autofagia / Uniones Estrechas / Beclina-1 / Mucosa Intestinal Límite: Animals / Female / Humans / Male Idioma: En Revista: Am J Physiol Cell Physiol Asunto de la revista: FISIOLOGIA Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autofagia / Uniones Estrechas / Beclina-1 / Mucosa Intestinal Límite: Animals / Female / Humans / Male Idioma: En Revista: Am J Physiol Cell Physiol Asunto de la revista: FISIOLOGIA Año: 2019 Tipo del documento: Article Pais de publicación: Estados Unidos