Redox-sensitivity of the dimerization of occludin |
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Authors: | J K Walter V Castro M Voss K Gast C Rueckert J Piontek Ingolf E Blasig |
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Institution: | 1. Leibniz-Institut für Molekulare Pharmakologie Berlin, FMP, Robert-R?ssle-Str. 10, 13125, Berlin-Buch, Germany 2. Institut für Biochemie und Biologie, Universit?t Potsdam, Potsdam, Germany
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Abstract: | Occludin is a self-associating transmembrane tight junction protein affected in oxidative stress. However, its function is
unknown. The cytosolic C-terminal tail contains a coiled coil-domain forming dimers contributing to the self-association.
Studying the hypothesis that the self-association is redox-sensitive, we found that the dimerization of the domain depended
on the sulfhydryl concentration of the environment in low-millimolar range. Under physiological conditions, monomers and dimers
were detected. Masking the sulfhydryl residues in the domain prevented the dimerization but affected neither its helical structure
nor cylindric shape. Incubation of cell extracts containing full-length occludin with sulfhydryl reagents prevented the dimerization;
a cysteine/alanine exchange mutant also did not show dimer formation. This demonstrates, for the first time, that disulfide
bridge formation of the domain is involved in the occludin dimerization. It is concluded that the redox-dependent dimerization
of occludin may play a regulatory role in the tight junction assembly under physiological and pathological conditions. |
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