Open AccessPhosphorylation hotspot in the C-terminal domain of occludin regulates the dynamics of epithelial junctional complexes
Author(s) -
Bhargavi Manda,
Hina Mir,
Ruchika Gangwar,
Avtar S. Meena,
Shrunali Amin,
Pradeep Kumar Shukla,
Kesha Dalal,
Takuya Suzuki,
Radhakrishna Rao
Publication year - 2018
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.206789
Subject(s) - occludin , adherens junction , tight junction , biology , microbiology and biotechnology , cell junction , phosphorylation , claudin , mutant , cadherin , cell , biochemistry , gene
The apical junctional complex (AJC), which includes tight junction (TJ) and adherens junction (AJ) determine the epithelial polarity, cell-cell adhesion and permeability barrier. An intriguing characteristic of TJ is the dynamic nature of its multiprotein complex. Occludin is the most mobile TJ protein, but its significance in TJ dynamics is poorly understood. On the basis of phosphorylation sites we distinguished a sequence in the C-terminal domain of occludin as a regulatory motif (ORM). Deletion of ORM and expression of deletion mutant occludin in renal and intestinal epithelia reduced the mobility of occludin at the TJ. ORM deletion attenuated Ca2+ depletion, osmotic stress and hydrogen peroxide-induced disruption of TJ, AJ and cytoskeleton. T403/404A, but not T403/404D, mutation in occludin mimicked the effect of ORM deletion on occludin mobility and AJC disruption by Ca2+-depletion. On the other hand, both Y398/402A and Y398/402D mutations partially blocked AJC disruption. Expression of deletion mutant occludin attenuated collective cell migration in the renal and intestinal epithelia. Overall, this study reveals the role of ORM and its phosphorylation in occludin mobility, AJC dynamics and epithelial cell migration.