QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Research Data Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wu, X. Articles by Brakebusch, C. Search for Related Content PubMed PubMed Citation Articles by Wu, X. Articles by Brakebusch, C. Social Bookmarking                   What's this?

RESEARCH PAPER

Cdc42 controls progenitor cell differentiation and -catenin turnover in skin

¹ Max Planck Institute of Biochemistry, Heisenberg Group "Regulation of Cytoskeletal Organization," Department of Molecular Medicine, 82152 Martinsried, Germany; ² Georg August University Göttingen, Department of Histology, 37075 Göttingen, Germany; ³ Max Planck Institute of Biochemistry, Department of Molecular Medicine, 82152 Martinsried, Germany; ⁴ University Hospital Schleswig-Holstein, Department of Dermatology, University of Lübeck, 23538 Lübeck, Germany; ⁵ Cell German Cancer Research Center, Department of Cell Biology, 69120 Heidelberg, Germany

Differentiation of skin stem cells into hair follicles (HFs) requires the inhibition of -catenin degradation, which is controlled by a complex containing axin and the protein kinase GSK3. Using conditional gene targeting in mice, we show now that the small GTPase Cdc42 is crucial for differentiation of skin progenitor cells into HF lineage and that it regulates the turnover of -catenin. In the absence of Cdc42, degradation of -catenin was increased corresponding to a decreased phosphorylation of GSK3 at Ser 9 and an increased phosphorylation of axin, which is known to be required for binding of -catenin to the degradation machinery. Cdc42-mediated regulation of -catenin turnover was completely dependent on PKC, which associated with Cdc42, Par6, and Par3. These data suggest that Cdc42 regulation of -catenin turnover is important for terminal differentiation of HF progenitor cells in vivo.

[Keywords: Rho GTPases; -catenin; keratinocytes]

Received August 2, 2005; revised version accepted January 12, 2006.

Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.361406.

⁶ Present address: Group of Developmental Biology, Institute of Molecular Pathology, Copenhagen University, 2100 Cophenhagen, Denmark.

⁷ Corresponding author.
E-MAIL cord{at}pai.ku.dk; FAX 45-353-26081.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				E. Fuchs and V. Horsley More than one way to skin . . . Genes & Dev., April 15, 2008; 22(8): 976 - 985. [Abstract] [Full Text] [PDF]

				B. K. Garvalov, K. C. Flynn, D. Neukirchen, L. Meyn, N. Teusch, X. Wu, C. Brakebusch, J. R. Bamburg, and F. Bradke Cdc42 Regulates Cofilin during the Establishment of Neuronal Polarity J. Neurosci., November 28, 2007; 27(48): 13117 - 13129. [Abstract] [Full Text] [PDF]

				R. L. Daugherty and C. J. Gottardi Phospho-regulation of {beta}-Catenin Adhesion and Signaling Functions Physiology, October 1, 2007; 22(5): 303 - 309. [Abstract] [Full Text] [PDF]

				Y. Benninger, T. Thurnherr, J. A. Pereira, S. Krause, X. Wu, A. Chrostek-Grashoff, D. Herzog, K.-A. Nave, R. J.M. Franklin, D. Meijer, et al. Essential and distinct roles for cdc42 and rac1 in the regulation of Schwann cell biology during peripheral nervous system development J. Cell Biol., July 30, 2007; 177(6): 1051 - 1061. [Abstract] [Full Text] [PDF]

				M. Kim, A. Datta, P. Brakeman, W. Yu, and K. E. Mostov Polarity proteins PAR6 and aPKC regulate cell death through GSK-3beta in 3D epithelial morphogenesis J. Cell Sci., July 15, 2007; 120(14): 2309 - 2317. [Abstract] [Full Text] [PDF]

				K. Kobielak, N. Stokes, J. de la Cruz, L. Polak, and E. Fuchs Loss of a quiescent niche but not follicle stem cells in the absence of bone morphogenetic protein signaling PNAS, June 12, 2007; 104(24): 10063 - 10068. [Abstract] [Full Text] [PDF]

				L. Yang, L. Wang, H. Geiger, J. A. Cancelas, J. Mo, and Y. Zheng Rho GTPase Cdc42 coordinates hematopoietic stem cell quiescence and niche interaction in the bone marrow PNAS, March 20, 2007; 104(12): 5091 - 5096. [Abstract] [Full Text] [PDF]

				K. Lefort, A. Mandinova, P. Ostano, V. Kolev, V. Calpini, I. Kolfschoten, V. Devgan, J. Lieb, W. Raffoul, D. Hohl, et al. Notch1 is a p53 target gene involved in human keratinocyte tumor suppression through negative regulation of ROCK1/2 and MRCK{alpha} kinases Genes & Dev., March 1, 2007; 21(5): 562 - 577. [Abstract] [Full Text] [PDF]

				L. Wang, L. Yang, M. Debidda, D. Witte, and Y. Zheng Cdc42 GTPase-activating protein deficiency promotes genomic instability and premature aging-like phenotypes PNAS, January 23, 2007; 104(4): 1248 - 1253. [Abstract] [Full Text] [PDF]

				L. Yang, L. Wang, and Y. Zheng Gene Targeting of Cdc42 and Cdc42GAP Affirms the Critical Involvement of Cdc42 in Filopodia Induction, Directed Migration, and Proliferation in Primary Mouse Embryonic Fibroblasts Mol. Biol. Cell, November 1, 2006; 17(11): 4675 - 4685. [Abstract] [Full Text] [PDF]

				T. Thurnherr, Y. Benninger, X. Wu, A. Chrostek, S. M. Krause, K.-A. Nave, R. J. M. Franklin, C. Brakebusch, U. Suter, and J. B. Relvas Cdc42 and Rac1 Signaling Are Both Required for and Act Synergistically in the Correct Formation of Myelin Sheaths in the CNS J. Neurosci., October 4, 2006; 26(40): 10110 - 10119. [Abstract] [Full Text] [PDF]

				Z. Xing, M. A. Ryan, D. Daria, K. J. Nattamai, G. Van Zant, L. Wang, Y. Zheng, and H. Geiger Increased hematopoietic stem cell mobilization in aged mice Blood, October 1, 2006; 108(7): 2190 - 2197. [Abstract] [Full Text] [PDF]