Abstract：
:Recently, we demonstrated in cultured endothelial cells and in vivo that deficiency of an isoform of intersectin-1, ITSN-1s, impairs caveolae and clathrin-mediated endocytosis and functionally upregulates compensatory pathways and their morphological carriers (i.e. enlarged endocytic structures, membranous rings or tubules) that are normally underrepresented. We now show that these endocytic structures internalize the broadly expressed transforming growth factor β receptor I (TGFβ-RI or TGFBR1), also known as Alk5, leading to its ubiquitylation and degradation. Moreover, the apoptotic or activated vascular cells of the ITSN-1s-knockdown mice release Alk5-bearing microparticles to the systemic circulation. These interact with and transfer Alk5 to endocytosis-deficient endothelial cells, resulting in lung endothelial cell survival and phenotypic alteration towards proliferation through activation of Erk1 and Erk2 (also known as MAPK3 and MAPK1, respectively). We also show that non-productive assembly of the Alk5-Smad-SARA (Smad anchor for receptor activation, also known as ZFYVE9) signaling complex and preferential formation of the Alk5-mSos-Grb2 complex account for Erk1/2 activation downstream of Alk5 and proliferation of pulmonary endothelial cells. Taken together, our studies demonstrate a functional relationship between the intercellular transfer of Alk5 by microparticles and endothelial cell survival and proliferation, and define a novel molecular mechanism for TGFβ and Alk5-dependent Erk1/2(MAPK) signaling that is significant for proliferative signaling and abnormal growth.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Bardita C,Predescu DN,Sha F,Patel M,Balaji G,Predescu SAdoi
10.1242/jcs.163030subject
Has Abstractpub_date
2015-04-15 00:00:00pages
1528-41issue
8eissn
0021-9533issn
1477-9137pii
jcs.163030journal_volume
128pub_type
杂志文章abstract：:The mechanisms by which volatile general anaesthetics (VAs) produce a depression of central nervous system are beginning to be better understood, but little is known about a number of side effects. Here, we show that the cold receptor transient receptor potential melastatin 8 (TRPM8) undergoes a complex modulation by ...
journal_title：Journal of cell science
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abstract：:We have discovered a novel mitosis-specific human autoantigen that arises at the centromeres of prophase chromosomes, but ultimately participates in formation of an organelle that bisects the cell at late anaphase and during telophase. The organelle, discernible as a three-dimensional disc by confocal microscopy, enco...
journal_title：Journal of cell science
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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
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journal_title：Journal of cell science
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journal_title：Journal of cell science
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doi：
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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：10.1242/jcs.031088
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journal_title：Journal of cell science
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更新日期：2014-12-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.129437
更新日期：2013-08-15 00:00:00
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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
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doi：
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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：
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journal_title：Journal of cell science
pub_type： 杂志文章
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