Phosphorylation of claudin-5 and occludin by rho kinase in brain endothelial cells

The American Journal of Pathology
Masaru YamamotoTsuneya Ikezu

Abstract

Critical to the proper maintenance of blood-brain-barrier (BBB) integrity are the endothelial tight junctions (TJs). Posttranslational modifications of essential endothelial TJ proteins, occludin and claudin-5, contribute and possibly disrupt BBB integrity. Our previous work has shown that Rho kinase (RhoK) activation mediates occludin and claudin-5 phosphorylation resulting in diminished barrier tightness and enhanced monocyte migration across BBB in the setting of human immunodeficiency virus-1 encephalitis (HIVE). To determine whether RhoK can directly phosphorylate TJ proteins, we examined phosphorylation of cytoplasmic domains of recombinant claudin-5 and occludin by RhoK. We found that RhoK predominately phosphorylated two sites on occludin (T382 and S507) and one site on claudin-5 (T207). Specific anti-phosphopeptide antibodies were developed for these sites, allowing the detection of phosphorylated occludin at T382 and S507, and claudin-5 at T207 from full-length recombinant occludin and claudin-5 transiently expressed in COS-7 cells and mouse brain microvascular endothelial cells. Finally, these phosphospecific antibodies demonstrated enhanced staining of brain endothelial cells in the mouse model for HIVE and human HI...Continue Reading

References

Oct 1, 1983·Physiological Reviews·W M Pardridge
Dec 1, 1993·The Journal of Cell Biology·M FuruseS Tsukita
Jun 16, 1997·The Journal of Cell Biology·A SakakibaraS Tsukita
Jan 20, 1999·Proceedings of the National Academy of Sciences of the United States of America·K MoritaS Tsukita
Nov 27, 1999·FEMS Immunology and Medical Microbiology·W E ZinkH E Gendelman
Sep 7, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·S Etienne-MannevilleP O Couraud
Dec 16, 2000·Arteriosclerosis, Thrombosis, and Vascular Biology·G P van Nieuw AmerongenV W van Hinsbergh
Aug 15, 2001·The Journal of Biological Chemistry·A Y AndreevaD I Utepbergenov
Apr 9, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Larisa Y PoluektovaHoward E Gendelman
Jan 18, 2003·Vascular Pharmacology·Hartwig Wolburg, Andrea Lippoldt
Feb 27, 2003·Biochemical and Biophysical Research Communications·G KaleR K Rao
Apr 18, 2003·American Journal of Physiology. Cell Physiology·Sandra van WeteringPeter L Hordijk
May 14, 2003·The Journal of Cell Biology·Takehiro NittaShoichiro Tsukita
Jun 7, 2003·Brain Research. Brain Research Reviews·Andrzej W Vorbrodt, Danuta H Dobrogowska
Jun 26, 2003·Experimental Dermatology·Kazumasa MoritaYoshiki Miyachi
Sep 24, 2004·Experimental Cell Research·Tamotsu SomaNorimasa Sawada
May 26, 2005·Pharmacological Reviews·Brian T Hawkins, Thomas P Davis
Jun 29, 2005·Atherosclerosis·Barbara E RolfeGordon R Campbell
May 11, 2006·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Georgette D KanmogneYuri Persidsky
Sep 16, 2006·Immunological Reviews·Yuri Persidsky, Larisa Poluektova
Sep 26, 2006·Journal of Cellular Physiology·Sumio OhtsukiTetsuya Terasaki

❮ Previous
Next ❯

Citations

Feb 4, 2010·Cellular and Molecular Neurobiology·Yoichi MorofujiMasami Niwa
Dec 12, 2012·Cellular and Molecular Neurobiology·Shoji HoraiMasami Niwa
Nov 27, 2008·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Howard E GendelmanHuangui Xiong
Jul 27, 2012·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Nicole A Northrop, Bryan K Yamamoto
Aug 31, 2012·Biochemistry·Elizabeth C LesseyKeith Burridge
Feb 19, 2011·Nature Reviews. Neuroscience·Edward A NeuweltLester R Drewes
Jun 20, 2012·Proceedings of the National Academy of Sciences of the United States of America·Brian R TashJohn M Flanagan
May 9, 2009·The Journal of Biological Chemistry·Svetlana M StamatovicAnuska V Andjelkovic
Mar 24, 2010·The Journal of Experimental Medicine·Rebecca A StocktonMark H Ginsberg
Jan 18, 2011·Antioxidants & Redox Signaling·Ingolf E BlasigReiner F Haseloff
Feb 1, 2011·Antioxidants & Redox Signaling·Christian E OvergaardMichael Koval
Feb 23, 2011·Antioxidants & Redox Signaling·Caroline Coisne, Britta Engelhardt
Nov 1, 2011·Pharmacological Reviews·C Yan Cheng, Dolores D Mruk
Jul 3, 2009·Journal of Virology·Lisa E GralinskiKatherine R Spindler
Nov 16, 2011·Molecular and Cellular Biology·Philip M Cummins
May 16, 2008·American Journal of Physiology. Renal Physiology·Susanne AngelowAlan S L Yu
Feb 9, 2012·Journal of Biomedicine & Biotechnology·Max Johannes Dörfel, Otmar Huber
Nov 13, 2012·Fluids and Barriers of the CNS·Anny-Claude LuissintPierre-Olivier Couraud
Mar 11, 2009·Frontiers in Bioscience (Landmark Edition)·Erika S Wittchen
Oct 18, 2012·Annual Review of Physiology·Michael Koval
Jan 9, 2013·The Journal of Cell Biology·Keith Burridge, Erika S Wittchen
May 8, 2010·Journal of Neuropathology and Experimental Neurology·Steven PetratosClaude C A Bernard
Feb 14, 2012·Gene Expression Patterns : GEP·Michelle M CollinsAimee K Ryan
Dec 14, 2011·Free Radical Biology & Medicine·Peter R Kvietys, D Neil Granger
Jun 28, 2011·Progress in Retinal and Eye Research·Lawrence J RizzoloWei Xiao
Jun 7, 2011·Brain Research·Marianne StrazzaMichael R Nonnemacher
Aug 6, 2010·Brain Research Reviews·Filipa Lourenço CardosoMaria Alexandra Brito
Sep 25, 2014·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Slava RomYuri Persidsky
Dec 2, 2008·Microvascular Research·Adel Boueiz, Paul M Hassoun
Sep 16, 2008·Neurobiology of Disease·Karin E Sandoval, Ken A Witt
Mar 26, 2009·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Yuji TakenagaSatoshi Takeo
May 21, 2015·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Keith D RochfortPhilip M Cummins
Jun 10, 2015·Biochemical and Biophysical Research Communications·Gretchen WolffMichal Toborek

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.