Advertisement
JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M204759200 on September 7, 2002

J. Biol. Chem., Vol. 277, Issue 49, 47399-47406, December 6, 2002
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
277/49/47399    most recent
M204759200v1
Right arrow Submit a Letter to Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
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 arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Behne, M. J.
Right arrow Articles by Mauro, T. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Behne, M. J.
Right arrow Articles by Mauro, T. 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  
What's this?

NHE1 Regulates the Stratum Corneum Permeability Barrier Homeostasis
MICROENVIRONMENT ACIDIFICATION ASSESSED WITH FLUORESCENCE LIFETIME IMAGING*

Martin J. BehneDagger §, Jamie W. Meyer||, Kerry M. Hanson**, Nicholas P. Barry**, Satoru MurataDagger , Debra CrumrineDagger , Robert W. Clegg**, Enrico Gratton**, Walter M. HolleranDagger , Peter M. EliasDagger , and Theodora M. MauroDagger

From the Dagger  Dermatology Service, Veterans Affairs Medical Center and Department of Dermatology, University of California, San Francisco, California 94121, the  Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, University of Cincinnati, Cincinnati, Ohio 45267, and the ** Laboratory for Fluorescence Dynamics, Department of Physics, University of Illinois, Urbana-Champaign, Illinois 61801

The outermost epidermal layer, the stratum corneum (SC), exhibits an acidic surface pH, whereas the pH at its base approaches neutrality. NHE1 is the only Na+/H+ antiporter isoform in keratinocytes and epidermis, and has been shown to regulate intracellular pH. We now demonstrate a novel function for NHE1, as we find that it also controls acidification of extracellular "microdomains" in the SC that are essential for activation of pH-sensitive enzymes and the formation of the epidermal permeability barrier. NHE1 expression in epidermis is most pronounced in granular cell layers, and although the surface pH of NHE1 knockout mice is only slightly more alkaline than normal using conventional pH measurements, a more sensitive method, fluorescence lifetime imaging, demonstrates that the acidic intercellular domains at the surface and of the lower SC disappear in NHE1 -/- animals. Fluorescence lifetime imaging studies also reveal that SC acidification does not occur through a uniform gradient, but through the progressive accumulation of acidic microdomains. These findings not only visualize the spatial distribution of the SC pH gradient, but also demonstrate a role for NHE1 in the generation of acidic extracellular domains of the lower SC, thus providing the acidification of deep SC interstices necessary for lipid processing and barrier homeostasis.

* This work was supported in part by National Institutes of Health Grants AR44341 (to T. M. M.), AR19098 (to P. M. E.), and Department of Veterans Affairs Merit Review MAU 3 "Creation and Maintenance of the Epidermal pH Gradient" (to T. M. M.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ Supported by a grant from Sebapharma, Boppard, Germany. To whom correspondence should be addressed: University of California San Francisco and Department of Veterans Affairs Medical Center, Dermatology Service (190), 4150 Clement St., San Francisco, CA 94121. E-mail: behnemj@itsa.ucsf.edu.

|| Supported in part by funds from National Institutes of Health Grant HL61974 (to Gary Shull).

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
R.-P. Charles, M. Guitard, C. Leyvraz, B. Breiden, M. Haftek, Z. Haftek-Terreau, J.-C. Stehle, K. Sandhoff, and E. Hummler
Postnatal Requirement of the Epithelial Sodium Channel for Maintenance of Epidermal Barrier Function
J. Biol. Chem., February 1, 2008; 283(5): 2622 - 2630.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
G. Yosipovitch, M. I. Duque, T. S. Patel, Y. Ishiuji, D. A. Guzman-Sanchez, A. G. Dawn, B. I. Freedman, Y. H. Chan, D. Crumrine, and P. M. Elias
Skin barrier structure and function and their relationship to pruritus in end-stage renal disease
Nephrol. Dial. Transplant., November 1, 2007; 22(11): 3268 - 3272.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
D. Ilic, M. Mao-Qiang, D. Crumrine, G. Dolganov, N. Larocque, P. Xu, M. Demerjian, B. E. Brown, S.-T. Lim, V. Ossovskaya, et al.
Focal Adhesion Kinase Controls pH-Dependent Epidermal Barrier Homeostasis by Regulating Actin-Directed Na+/H+ Exchanger 1 Plasma Membrane Localization
Am. J. Pathol., June 1, 2007; 170(6): 2055 - 2067.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
C. Graham, I. Gatherar, I. Haslam, M. Glanville, and N. L. Simmons
Expression and localization of monocarboxylate transporters and sodium/proton exchangers in bovine rumen epithelium
Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2007; 292(2): R997 - R1007.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
D. Piwnica, I. Fernandez, N. Binart, P. Touraine, P. A. Kelly, and V. Goffin
A New Mechanism for Prolactin Processing into 16K PRL by Secreted Cathepsin D
Mol. Endocrinol., December 1, 2006; 20(12): 3263 - 3278.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
E. Houben, W. M. Holleran, T. Yaginuma, C. Mao, L. M. Obeid, V. Rogiers, Y. Takagi, P. M. Elias, and Y. Uchida
Differentiation-associated expression of ceramidase isoforms in cultured keratinocytes and epidermis
J. Lipid Res., May 1, 2006; 47(5): 1063 - 1070.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
Advertisement
spacer
Advertisement
Advertisement