Occludin

OCLN
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesOCLN, BLCPMG, PPP1R115, occludin, PTORCH1
External IDsOMIM: 602876; MGI: 106183; HomoloGene: 1905; GeneCards: OCLN; OMA:OCLN - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_002538
NM_001205254
NM_001205255

NM_008756
NM_001360536
NM_001360537
NM_001360538
NM_001360539

RefSeq (protein)

NP_001192183
NP_001192184
NP_002529

NP_032782
NP_001347465
NP_001347466
NP_001347467
NP_001347468

Location (UCSC)Chr 5: 69.49 – 69.56 MbChr 13: 100.63 – 100.69 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse
Diagram of Tight junction.

Occludin is a transmembrane protein that regulates the permeability of epithelial and endothelial barriers. It was first identified in epithelial cells as a 65 kDa integral plasma-membrane protein localized at the tight junctions.[5] Together with Claudins, and zonula occludens-1 (ZO-1), occludin has been considered a staple of tight junctions, and although it was shown to regulate the formation, maintenance, and function of tight junctions, its precise mechanism of action remained elusive and most of its actions were initially attributed to conformational changes following selective phosphorylation,[6] and its redox-sensitive dimerization.[7][8] However, mounting evidence demonstrated that occludin is not only present in epithelial/endothelial cells, but is also expressed in large quantities in cells that do not have tight junctions but have very active metabolism: pericytes,[9] neurons and astrocytes,[10] oligodendrocytes,[11] dendritic cells,[12] monocytes/macrophages[13] lymphocytes,[14] and myocardium.[15] Recent work, using molecular modeling, supported by biochemical and live-cell experiments in human cells demonstrated that occludin is a NADH oxidase that influences critical aspects of cell metabolism like glucose uptake, ATP production and gene expression.[16] Furthermore, manipulation of occludin content in human cells is capable of influencing the expression of glucose transporters,[16] and the activation of transcription factors like NFkB, and histone deacetylases like sirtuins, which proved capable of diminishing HIV replication rates in infected human macrophages under laboratory conditions.[9]

  1. ^ a b c ENSG00000273814 GRCh38: Ensembl release 89: ENSG00000197822, ENSG00000273814Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021638Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Furuse M, Hirase T, Itoh M, Nagafuchi A, Yonemura S, Tsukita S, Tsukita S (December 1993). "Occludin: a novel integral membrane protein localizing at tight junctions". The Journal of Cell Biology. 123 (6 Pt 2): 1777–88. doi:10.1083/jcb.123.6.1777. PMC 2290891. PMID 8276896.
  6. ^ Blasig IE, Bellmann C, Cording J, Del Vecchio G, Zwanziger D, Huber O, Haseloff RF (September 2011). "Occludin protein family: oxidative stress and reducing conditions". Antioxidants & Redox Signaling. 15 (5): 1195–219. doi:10.1089/ars.2010.3542. PMID 21235353.
  7. ^ Walter JK, Castro V, Voss M, Gast K, Rueckert C, Piontek J, Blasig IE (November 2009). "Redox-sensitivity of the dimerization of occludin". Cellular and Molecular Life Sciences. 66 (22): 3655–62. doi:10.1007/s00018-009-0150-z. PMC 11115754. PMID 19756380. S2CID 23090886.
  8. ^ Villela C, Manuel V (2011). "The interplay between occludin and ZO-1 is redox sensitive". doi:10.17169/refubium-12742. {{cite journal}}: Cite journal requires |journal= (help)
  9. ^ a b Castro V, Bertrand L, Luethen M, Dabrowski S, Lombardi J, Morgan L, et al. (March 2016). "Occludin controls HIV transcription in brain pericytes via regulation of SIRT-1 activation". FASEB Journal. 30 (3): 1234–46. doi:10.1096/fj.15-277673. PMC 4750406. PMID 26601824.
  10. ^ Bauer H, Stelzhammer W, Fuchs R, Weiger TM, Danninger C, Probst G, Krizbai IA (August 1999). "Astrocytes and neurons express the tight junction-specific protein occludin in vitro". Experimental Cell Research. 250 (2): 434–8. doi:10.1006/excr.1999.4558. PMID 10413597.
  11. ^ Romanitan MO, Popescu BO, Winblad B, Bajenaru OA, Bogdanovic N (2007). "Occludin is overexpressed in Alzheimer's disease and vascular dementia". Journal of Cellular and Molecular Medicine. 11 (3): 569–79. doi:10.1111/j.1582-4934.2007.00047.x. PMC 3922362. PMID 17635647.
  12. ^ Rescigno M, Rotta G, Valzasina B, Ricciardi-Castagnoli P (December 2001). "Dendritic cells shuttle microbes across gut epithelial monolayers". Immunobiology. 204 (5): 572–81. doi:10.1078/0171-2985-00094. PMID 11846220.
  13. ^ Castro V, Bertrand L, Luethen M, Dabrowski S, Lombardi J, Morgan L, et al. (March 2016). "Occludin controls HIV transcription in brain pericytes via regulation of SIRT-1 activation". FASEB Journal. 30 (3): 1234–46. doi:10.1096/fj.15-277673. PMC 4750406. PMID 26601824.
  14. ^ Alexander JS, Dayton T, Davis C, Hill S, Jackson TH, Blaschuk O, et al. (December 1998). "Activated T-lymphocytes express occludin, a component of tight junctions". Inflammation. 22 (6): 573–82. doi:10.1023/a:1022310429868. PMID 9824772. S2CID 23713562.
  15. ^ Qiu L, Chen C, Ding G, Zhou Y, Zhang M (August 2011). "The effects of electromagnetic pulse on the protein levels of tight junction associated-proteins in the cerebral cortex, hippocampus, heart, lung, and testis of rats". Biomedical and Environmental Sciences. 24 (4): 438–44. Bibcode:2011BioES..24..438Q. doi:10.3967/0895-3988.2011.04.016. PMID 22108334.
  16. ^ a b Castro V, Skowronska M, Lombardi J, He J, Seth N, Velichkovska M, Toborek M (February 2018). "Occludin regulates glucose uptake and ATP production in pericytes by influencing AMP-activated protein kinase activity". Journal of Cerebral Blood Flow and Metabolism. 38 (2): 317–332. doi:10.1177/0271678X17720816. PMC 5951017. PMID 28718701.