Occludin phosphorylation in regulation of epithelial tight junctions.
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 Ser/Thr 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, PKCzeta, and PKClambda/iota, 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 Ser/Thr/Tyr 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.
Rao
Radhakrishna
R
Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA. rkrao@physio1.utmem.edu
D000818:Animals; D001665:Binding Sites; D004848:Epithelium / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D062793:Occludin; D010766:Phosphorylation; D012694:Serine / Q000235:genetics / Q000378:metabolism; D013912:Threonine / Q000235:genetics / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism*; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism
D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; C568986:Ocln protein, mouse; D013912:Threonine; D014443:Tyrosine; D012694:Serine