Intestinal Epithelial Tight Junction Barrier regulation by Autophagy related protein ATG6/beclin 1.

Intestinal Epithelial Tight Junction Barrier regulation by Autophagy related protein ATG6/beclin 1. Am J Physiol Cell Physiol. 2019 Mar 20;: Authors: Wong M, Ganapathy AS, Suchanec E, Laidler L, Ma T, Nighot PK Abstract 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 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 intestinal TJ barrier is not known. In Caco-2 cells, beclin 1 was found to be co-immunoprecipitated with the TJ protein occludin and co-localized with occludin on the membrane. Treatment of Caco-2 cells with beclin 1 peptide (Tat-beclin 1) reduced TJ barrier function. Activation of beclin 1 increased occludin endocytosis and reduced total occludin protein level. On the contrary, 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, ...
Source: Am J Physiol Cell Ph... - Category: Cytology Authors: Tags: Am J Physiol Cell Physiol Source Type: research