Occludin phosphorylation in regulation of epithelial tight junctions

Research output: Chapter in Book/Report/Conference proceedingChapter

108 Citations (Scopus)

Abstract

Occludin is the first transmembrane protein of the tight junction to be discovered. While numerous studies emphasized the important role of occludin in assembly and maintenance of tight junctions, occludin knockout studies indicated that it was not required for tight junction assembly in different epithelia. However, a detailed characterization of the occludin knockout mouse concluded that the occludin gene is indispensable, and plays a complex role in regulation of epithelial tight junctions in different organs. This article describes the role of occludin phosphorylation in the regulation of its assembly into the tight junctions. Occludin is highly phosphorylated on Ser and Thr residues, while Tyr-phosphorylation is kept at minimum in the intact epithelium. During the disruption of tight junctions by various factors, occludin undergoes dephosphorylation on SerThr residues and elevated phosphorylation on Tyr residues. The phosphorylation of occludin on Tyr, Ser, and Thr residues appears to be regulated by the balance between protein kinases such as c-Src, PKCζ, and PKCλι, and protein phosphatases such as PP2A, PP1, and PTP1B. The precise mechanism of regulation of the tight junction by occludin phosphorylation is unclear at this time. However, an in vitro study indicated that Tyr-phosphorylation of occludin C-terminal domain attenuates its interaction with ZO-1. Therefore, phosphorylation of specific SerThrTyr residues in occludin may regulate its interactions with ZO-1 and possibly other tight junction proteins. It is likely that occludin plays a regulatory role in tight junctions rather than a role in the de novo assembly of tight junctions.

Original languageEnglish (US)
Title of host publicationMolecular Structure and Function of the Tight Junction From Basic Mechanisms to Clinical Manifestations
PublisherBlackwell Publishing Inc.
Pages62-68
Number of pages7
ISBN (Print)9781573317498
DOIs
StatePublished - Jan 1 2009

Publication series

NameAnnals of the New York Academy of Sciences
Volume1165
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Fingerprint

Occludin
Phosphorylation
Tight Junctions
Tight Junction Proteins
Epithelium
Protein
Phosphoprotein Phosphatases
Knockout Mice
Protein Kinases

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

Cite this

Rao, R. (2009). Occludin phosphorylation in regulation of epithelial tight junctions. In Molecular Structure and Function of the Tight Junction From Basic Mechanisms to Clinical Manifestations (pp. 62-68). (Annals of the New York Academy of Sciences; Vol. 1165). Blackwell Publishing Inc.. https://doi.org/10.1111/j.1749-6632.2009.04054.x

Occludin phosphorylation in regulation of epithelial tight junctions. / Rao, Radhakrishna.

Molecular Structure and Function of the Tight Junction From Basic Mechanisms to Clinical Manifestations. Blackwell Publishing Inc., 2009. p. 62-68 (Annals of the New York Academy of Sciences; Vol. 1165).

Research output: Chapter in Book/Report/Conference proceedingChapter

Rao, R 2009, Occludin phosphorylation in regulation of epithelial tight junctions. in Molecular Structure and Function of the Tight Junction From Basic Mechanisms to Clinical Manifestations. Annals of the New York Academy of Sciences, vol. 1165, Blackwell Publishing Inc., pp. 62-68. https://doi.org/10.1111/j.1749-6632.2009.04054.x
Rao R. Occludin phosphorylation in regulation of epithelial tight junctions. In Molecular Structure and Function of the Tight Junction From Basic Mechanisms to Clinical Manifestations. Blackwell Publishing Inc. 2009. p. 62-68. (Annals of the New York Academy of Sciences). https://doi.org/10.1111/j.1749-6632.2009.04054.x
Rao, Radhakrishna. / Occludin phosphorylation in regulation of epithelial tight junctions. Molecular Structure and Function of the Tight Junction From Basic Mechanisms to Clinical Manifestations. Blackwell Publishing Inc., 2009. pp. 62-68 (Annals of the New York Academy of Sciences).
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