Abstract：
:The polarized functions of epithelia require an intact tight junction (TJ) to restrict paracellular movement and to separate membrane proteins into specific domains. TJs contain scaffolding, integral membrane and signaling proteins, but the mechanisms that regulate TJs and their assembly are not well defined. Galpha12 (GNA12) binds the TJ protein ZO-1 (TJP1), and Galpha12 activates Src to increase paracellular permeability via unknown mechanisms. Herein, we identify Src as a component of the TJ and find that recruitment of Hsp90 to activated Galpha12 is necessary for signaling. TJ integrity is disrupted by Galpha12-stimulated Src phosphorylation of ZO-1 and ZO-2 (TJP2); this phosphorylation leads to dissociation of occludin and claudin 1 from the ZO-1 protein complex. Inhibiting Hsp90 with geldanamycin blocks Galpha12-stimulated Src activation and phosphorylation, but does not affect protein levels or the Galpha12-ZO-1 interaction. Using the calcium-switch model of TJ assembly and GST-TPR (GST-fused TPR domain of PP5) pull-downs of activated Galpha12, we demonstrate that switching to normal calcium medium activates endogenous Galpha12 during TJ assembly. Thrombin increases permeability and delays TJ assembly by activating Galpha12, but not Galpha13, signaling pathways. These findings reveal an important role for Galpha12, Src and Hsp90 in regulating the TJ in established epithelia and during TJ assembly.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Sabath E,Negoro H,Beaudry S,Paniagua M,Angelow S,Shah J,Grammatikakis N,Yu AS,Denker BMdoi
10.1242/jcs.014878subject
Has Abstractpub_date
2008-03-15 00:00:00pages
814-24issue
Pt 6eissn
0021-9533issn
1477-9137pii
jcs.014878journal_volume
121pub_type
杂志文章abstract：:Schizosaccharomyces pombe cells divide by medial fission throughout contraction of an actomyosin ring and deposition of a multilayered division septum that must be cleaved to release the two daughter cells. Although many studies have focused on the actomoysin ring and septum assembly, little information is available c...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.00377
更新日期：2003-05-01 00:00:00
abstract：:The development of the phosphorylase-glycogen complex was studied in cells of the myogenic line L6 at different stages of differentiation. Our results indicate that the complex is already present in mononucleated myoblasts. However, several features of the complex observed in the myoblasts, such as the total amount of...
journal_title：Journal of cell science
pub_type： 杂志文章
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更新日期：1977-08-01 00:00:00
abstract：:We have isolated suppressors of the deletion allele of delta-tubulin, uni3-1, in the biflagellate green alga Chlamydomonas reinhardtii. The deletion of delta-tubulin produces cells that assemble zero, one or two flagella and have basal bodies composed primarily of doublet rather than triplet microtubules. Flagellar nu...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.00859
更新日期：2004-01-15 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2001-01-01 00:00:00
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journal_title：Journal of cell science
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.065698
更新日期：2010-04-15 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.098087
更新日期：2012-04-15 00:00:00
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更新日期：2017-07-15 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1998-03-01 00:00:00
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pub_type： 杂志文章
doi：10.1242/jcs.078055
更新日期：2011-03-15 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.113423
更新日期：2012-11-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1993-04-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1976-12-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章,评审
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更新日期：2004-01-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1990-08-01 00:00:00
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pub_type： 杂志文章,评审
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更新日期：2020-09-09 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.036673
更新日期：2009-01-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1997-04-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
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更新日期：2006-05-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1994-02-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1988-05-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
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更新日期：2013-10-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1991-09-01 00:00:00
abstract：:How vesicle trafficking components actively contribute to regulation of paracrine signaling is unclear. We genetically uncovered a requirement for α-soluble NSF attachment protein (α-Snap) in the activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway during Drosophila egg de...
journal_title：Journal of cell science
pub_type： 杂志文章
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更新日期：2018-11-30 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章,评审
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更新日期：2013-06-15 00:00:00
abstract：:Mammalian melanocytes can produce two basic types of melanin, eumelanin and pheomelanin, within discrete organelles termed melanosomes. The physiological signals that regulate this switch are extrinsic to the melanocyte, and include alpha-melanocyte stimulating hormone and the agouti protein. Tyrosinase, encoded at th...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1995-06-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
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更新日期：2019-12-02 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1986-12-01 00:00:00
