spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

First published online May 20, 2009
doi: 10.1242/10.1242/jcs.038729

Journal of Cell Science 122, 1863-1871 (2009)
Published by The Company of Biologists 2009
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chen, C.-L.
Right arrow Articles by Huang, J. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chen, C.-L.
Right arrow Articles by Huang, J. S.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Research Article

Inhibitors of clathrin-dependent endocytosis enhance TGFβ signaling and responses

Chun-Lin Chen1, Wei-Hsien Hou1, I-Hua Liu1, George Hsiao2, Shuan Shian Huang3,4,* and Jung San Huang1,5,*

1 Departments of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, Doisy Research Center, St Louis, MO 63104, USA
2 Department of Pharmacology, Taipei Medical University, Taipei, Taiwan
3 Auxagen, St Louis, MO 63132, USA
4 Center for Biotechnology and Biomedical Engineering, National Central University, Jhongli, Taiwan
5 Institute of Systems Biology and Bioinformatics, National Central University, Jhongli, Taiwan

* Authors for correspondence (e-mails: shuanh{at}gmail.com; huangjs{at}slu.edu)

Accepted 17 February 2009

Clathrin-dependent endocytosis is believed to be involved in TGFβ-stimulated cellular responses, but the subcellular locus at which TGFβ induces signaling remains unclear. Here, we demonstrate that inhibitors of clathrin-dependent endocytosis, which are known to arrest the progression of endocytosis at coated-pit stages, inhibit internalization of cell-surface-bound TGFβ and promote colocalization and accumulation of TβR-I and SARA at the plasma membrane. These inhibitors enhance TGFβ-induced signaling and cellular responses (Smad2 phosphorylation/nuclear localization and expression of PAI-1). Dynasore, a newly identified inhibitor of dynamin GTPase activity, is one of the most potent inhibitors among those tested and, furthermore, is a potent enhancer of TGFβ. Dynasore ameliorates atherosclerosis in the aortic endothelium of hypercholesterolemic ApoE-null mice by counteracting the suppressed TGFβ responsiveness caused by the hypercholesterolemia, presumably acting through its effect on TGFβ endocytosis and signaling in vascular cells.

Key words: Endocytosis inhibitor, TGFβ, Coated pit, Signaling, Enhancer, Atherosclerosis


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 DevelopmentHome page
A. I. Hagemann, X. Xu, O. Nentwich, M. Hyvonen, and J. C. Smith
Rab5-mediated endocytosis of activin is not required for gene activation or long-range signalling in Xenopus
Development, August 15, 2009; 136(16): 2803 - 2813.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2009