title: The ubiquitin-proteasome pathway regulates claudin 5 degradation.
abstract: The tight junctions (TJs) form continuous intracellular contacts, which help create selective barriers in epithelial and endothelial cell layers. The structures created by the TJs are very dynamic and can be rapidly remodeled in response to physiological and pathological signals. Claudin 5 is a membranal TJ protein which plays a critical role in determining the permeability of endothelial barriers. We describe the regulation of claudin 5 degradation by the ubiquitin-proteasome system (UPS). Our results indicate that claudin 5 has a relatively short half-life and can be polyubiquitinated on lysine 199. This ubiquitination appears to trigger the proteasome-dependent degradation of claudin 5. Other mechanisms also seem to be involved in the post-translational regulation of claudin 5, including a ubiquitin-independent and probably indirect lysosomal-dependent pathway. These findings provide evidence for the involvement of the UPS in the regulation of claudin 5 levels, and set the stage for further research to determine the involvement of this pathway in the modulation of the properties of TJs and cell-layer barriers.
authors.affiliation: Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Ilana
authors.initials: I
authors.lastname: Mandel
authors.forename: Tamar
authors.initials: T
authors.lastname: Paperna
authors.forename: Anat
authors.initials: A
authors.lastname: Volkowich
authors.forename: Maayan
authors.initials: M
authors.lastname: Merhav
authors.forename: Lea
authors.initials: L
authors.lastname: Glass-Marmor
authors.forename: Ariel
authors.initials: A
authors.lastname: Miller
mesh_terms: D045744:Cell Line, Tumor; D062507:Claudin-5; D057167:Claudins / Q000378:metabolism*; D006367:HeLa Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D019108:Tight Junctions / Q000502:physiology; D025801:Ubiquitin / Q000378:metabolism; D054875:Ubiquitination / Q000502:physiology*
chemical_list: C107466:CLDN5 protein, human; D062507:Claudin-5; D057167:Claudins; D008565:Membrane Proteins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex