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


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search    

The fully linked HTML version of this article has now been published.
Development ePress online publication date 29 Aug 2007
doi: 10.1242/dev.004556

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dev.004556v1
134/19/3461    most recent
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 Carney, T. J.
Right arrow Articles by Hammerschmidt, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Carney, T. J.
Right arrow Articles by Hammerschmidt, M.
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

Inactivation of serine protease Matriptase1a by its inhibitor Hai1 is required for epithelial integrity of the zebrafish epidermis


Thomas J. Carney, Sophia von der Hardt, Carmen Sonntag, Adam Amsterdam, Jacek Topczewski, Nancy Hopkins, and Matthias Hammerschmidt*
* Author for correspondence (e-mail: hammerschmid{at}immunbio.mpg.de)

Epithelial integrity requires the adhesion of cells to each other as well as to an underlying basement membrane. The modulation of adherence properties is crucial to morphogenesis and wound healing, and deregulated adhesion has been implicated in skin diseases and cancer metastasis. Here, we describe zebrafish that are mutant in the serine protease inhibitor Hai1a (Spint1la), which display disrupted epidermal integrity. These defects are further enhanced upon combined loss of hai1a and its paralog hai1b. By applying in vivo imaging, we demonstrate that Hai1-deficient keratinocytes acquire mesenchymal-like characteristics, lose contact with each other, and become mobile and more susceptible to apoptosis. In addition, inflammation of the mutant skin is evident, although not causative of the epidermal defects. Only later, the epidermis exhibits enhanced cell proliferation. The defects of hai1 mutants can be phenocopied by overexpression and can be fully rescued by simultaneous inactivation of the serine protease Matriptase1a (St14a), indicating that Hai1 promotes epithelial integrity by inhibiting Matriptase1a. By contrast, Hepatocyte growth factor (Hgf), a well-known promoter of epithelial-mesenchymal transitions and a prime target of Matriptase1 activity, plays no major role. Our work provides direct genetic evidence for antagonistic in vivo roles of Hai1 and Matriptase1a to regulate skin homeostasis and remodeling.


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
R. Szabo, J. P. Hobson, K. Christoph, P. Kosa, K. List, and T. H. Bugge
Regulation of cell surface protease matriptase by HAI2 is essential for placental development, neural tube closure and embryonic survival in mice
Development, August 1, 2009; 136(15): 2653 - 2663.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
J.-K. Wang, M.-S. Lee, I-C. Tseng, F.-P. Chou, Y.-W. Chen, A. Fulton, H.-S. Lee, C.-J. Chen, M. D. Johnson, and C.-Y. Lin
Polarized epithelial cells secrete matriptase as a consequence of zymogen activation and HAI-1-mediated inhibition
Am J Physiol Cell Physiol, August 1, 2009; 297(2): C459 - C470.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
M. E. Dodd, J. Hatzold, J. R. Mathias, K. B. Walters, D. A. Bennin, J. Rhodes, J. P. Kanki, A. T. Look, M. Hammerschmidt, and A. Huttenlocher
The ENTH domain protein Clint1 is required for epidermal homeostasis in zebrafish
Development, August 1, 2009; 136(15): 2591 - 2600.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
H. Cheng, T. Fukushima, N. Takahashi, H. Tanaka, and H. Kataoka
Hepatocyte Growth Factor Activator Inhibitor Type 1 Regulates Epithelial to Mesenchymal Transition through Membrane-Bound Serine Proteinases
Cancer Res., March 1, 2009; 69(5): 1828 - 1835.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
K. Nagaike, M. Kawaguchi, N. Takeda, T. Fukushima, A. Sawaguchi, K. Kohama, M. Setoyama, and H. Kataoka
Defect of Hepatocyte Growth Factor Activator Inhibitor Type 1/Serine Protease Inhibitor, Kunitz Type 1 (Hai-1/Spint1) Leads to Ichthyosis-Like Condition and Abnormal Hair Development in Mice
Am. J. Pathol., November 1, 2008; 173(5): 1464 - 1475.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. Szabo, J. P. Hobson, K. List, A. Molinolo, C.-Y. Lin, and T. H. Bugge
Potent Inhibition and Global Co-localization Implicate the Transmembrane Kunitz-type Serine Protease Inhibitor Hepatocyte Growth Factor Activator Inhibitor-2 in the Regulation of Epithelial Matriptase Activity
J. Biol. Chem., October 24, 2008; 283(43): 29495 - 29504.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
I-C. Tseng, F.-P. Chou, S.-F. Su, M. Oberst, N. Madayiputhiya, M.-S. Lee, J.-K. Wang, D. E. Sloane, M. Johnson, and C.-Y. Lin
Purification from human milk of matriptase complexes with secreted serpins: mechanism for inhibition of matriptase other than HAI-1
Am J Physiol Cell Physiol, August 1, 2008; 295(2): C423 - C431.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
K. Laue, S. Daujat, J. G. Crump, N. Plaster, H. H. Roehl, Tubingen 2000 Screen Consortium, C. B. Kimmel, R. Schneider, and M. Hammerschmidt
The multidomain protein Brpf1 binds histones and is required for Hox gene expression and segmental identity
Development, June 1, 2008; 135(11): 1935 - 1946.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2007