| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,2
,4
* Institut für Molekulare Medizin und Zellforschung, Albert Ludwigs Universität Freiburg, 79106 Freiburg, Germany;
Hautklinik, Charité, Humboldt Universität, 10117 Berlin, Germany;
Abteilung Biochemie II, Zentrum Biochemie und Molekulare Zellbiologie, Georg August Universität Göttingen, 37073 Göttingen, Germany;
§ Allgemeine Pathologie und Neuropathologie, Tierärztliche Fakultät der Ludwig Maximilians Universität München, 80539 München, Germany; and
¶ Institut für Ultrastrukturforschung der Haut, Hautklinik der Ruprecht Karls Universität Heidelberg, 69115 Heidelberg, Germany
5Correspondence: Institut für Molekulare Medizin und Zellforschung, Albert Ludwigs Universität Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany. E-mail: petersc{at}mm11.ukl.uni-freiburg.de
Lysosomal cysteine proteinases of the papain family are involved in lysosomal bulk proteolysis, major histocompatibility complex class II mediated antigen presentation, prohormone processing, and extracellular matrix remodeling. Cathepsin L (CTSL) is a ubiquitously expressed major representative of the papain-like family of cysteine proteinases. To investigate CTSL in vivo functions, the gene was inactivated by gene targeting in embryonic stem cells. CTSL-deficient mice develop periodic hair loss and epidermal hyperplasia, acanthosis, and hyperkeratosis. The hair loss is due to alterations of hair follicle morphogenesis and cycling, dilatation of hair follicle canals, and disturbed club hair formation. Hyperproliferation of hair follicle epithelial cells and basal epidermal keratinocytes—both of ectodermal origin—are the primary characteristics underlying the mutant phenotype. Pathological inflammatory responses have been excluded as a putative cause of the skin and hair disorder. The phenotype of CTSL-deficient mice is reminiscent of the spontaneous mouse mutant furless (fs). Analyses of the ctsl gene of fs mice revealed a G149R mutation inactivating the proteinase activity. CTSL is the first lysosomal proteinase shown to be essential for epidermal homeostasis and regular hair follicle morphogenesis and cycling.—Roth, W., Deussing, J., Botchkarev, V. A., Pauly-Evers, M., Saftig, P., Hafner, A., Schmidt, P., Schmahl, W., Scherer, J., Anton-Lamprecht, I., von Figura, K., Paus, R., Peters, C. Cathepsin L deficiency as molecular defect of furless: hyperproliferation of keratinocytes and pertubation of hair follicle cycling.
Key Words: epidermal hyperplasia • hair follicle development • lysosomal cysteine proteinase
This article has been cited by other articles:
|
|
 |
|
  D. Spira, J. Stypmann, D. J. Tobin, I. Petermann, C. Mayer, S. Hagemann, O. Vasiljeva, T. Gunther, R. Schule, C. Peters, et al. Cell Type-specific Functions of the Lysosomal Protease Cathepsin L in the Heart J. Biol. Chem., December 21, 2007; 282(51): 37045 - 37052. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Boudreau, C. R. Lussier, S. Mongrain, M. Darsigny, J. L. Drouin, G. Doyon, E. R. Suh, J.-F. Beaulieu, N. Rivard, and N. Perreault Loss of cathepsin L activity promotes claudin-1 overexpression and intestinal neoplasia FASEB J, December 1, 2007; 21(14): 3853 - 3865. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Lu, J. Qian, D. Keppler, and W. V. Cardoso Cathespin H Is an Fgf10 Target Involved in Bmp4 Degradation during Lung Branching Morphogenesis J. Biol. Chem., July 27, 2007; 282(30): 22176 - 22184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Lecaille, S. Chowdhury, E. Purisima, D. Bromme, and G. Lalmanach The S2 subsites of cathepsins K and L and their contribution to collagen degradation Protein Sci., April 1, 2007; 16(4): 662 - 670. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Cheng, K. Hitomi, I. M. J. J. van Vlijmen-Willems, G. J. de Jongh, K. Yamamoto, K. Nishi, C. Watts, T. Reinheckel, J. Schalkwijk, and P. L. J. M. Zeeuwen Cystatin M/E Is a High Affinity Inhibitor of Cathepsin V and Cathepsin L by a Reactive Site That Is Distinct from the Legumain-binding Site: A NOVEL CLUE FOR THE ROLE OF CYSTATIN M/E IN EPIDERMAL CORNIFICATION J. Biol. Chem., June 9, 2006; 281(23): 15893 - 15899. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. A. Bulynko, L. C. Hsing, R. W. Mason, D. J. Tremethick, and S. A. Grigoryev Cathepsin L stabilizes the histone modification landscape on the y chromosome and pericentromeric heterochromatin. Mol. Cell. Biol., June 1, 2006; 26(11): 4172 - 4184. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Petermann, C. Mayer, J. Stypmann, M. L. Biniossek, D. J. Tobin, M. A. Engelen, T. Dandekar, T. Grune, L. Schild, C. Peters, et al. Lysosomal, cytoskeletal, and metabolic alterations in cardiomyopathy of cathepsin L knockout mice FASEB J, June 1, 2006; 20(8): 1266 - 1268. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Gocheva, W. Zeng, D. Ke, D. Klimstra, T. Reinheckel, C. Peters, D. Hanahan, and J. A. Joyce Distinct roles for cysteine cathepsin genes in multistage tumorigenesis Genes & Dev., March 1, 2006; 20(5): 543 - 556. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Shacka and K. A. Roth Cathepsin Deficiency as a Model for Neuronal Ceroid Lipofuscinoses Am. J. Pathol., December 1, 2005; 167(6): 1473 - 1476. [Full Text] [PDF]
|
|
|
|
 |
|
 C. T. Pager and R. E. Dutch Cathepsin L Is Involved in Proteolytic Processing of the Hendra Virus Fusion Protein J. Virol., October 15, 2005; 79(20): 12714 - 12720. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Reinheckel, S. Hagemann, S. Dollwet-Mack, E. Martinez, T. Lohmuller, G. Zlatkovic, D. J. Tobin, N. Maas-Szabowski, and C. Peters The lysosomal cysteine protease cathepsin L regulates keratinocyte proliferation by control of growth factor recycling J. Cell Sci., August 1, 2005; 118(15): 3387 - 3395. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Lombardi, D. Burzyn, J. Mundinano, P. Berguer, P. Bekinschtein, H. Costa, L. F. Castillo, A. Goldman, R. Meiss, I. Piazzon, et al. Cathepsin-L Influences the Expression of Extracellular Matrix in Lymphoid Organs and Plays a Role in the Regulation of Thymic Output and of Peripheral T Cell Number J. Immunol., June 1, 2005; 174(11): 7022 - 7032. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Maehr, H. C. Hang, J. D. Mintern, Y.-M. Kim, A. Cuvillier, M. Nishimura, K. Yamada, K. Shirahama-Noda, I. Hara-Nishimura, and H. L. Ploegh Asparagine Endopeptidase Is Not Essential for Class II MHC Antigen Presentation but Is Required for Processing of Cathepsin L in Mice J. Immunol., June 1, 2005; 174(11): 7066 - 7074. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Nishikawa Presence of Anti-cystatin C-positive Dendritic Cells or Macrophages and Localization of Cysteine Proteases in the Apical Bud of the Enamel Organ in the Rat Incisor J. Histochem. Cytochem., May 1, 2005; 53(5): 643 - 651. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Henningsson, K. Yamamoto, P. Saftig, T. Reinheckel, C. Peters, S. D. Knight, and G. Pejler A role for cathepsin E in the processing of mast-cell carboxypeptidase A J. Cell Sci., May 1, 2005; 118(9): 2035 - 2042. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Beers, A. Burich, M. J. Kleijmeer, J. M. Griffith, P. Wong, and A. Y. Rudensky Cathepsin S Controls MHC Class II-Mediated Antigen Presentation by Epithelial Cells In Vivo J. Immunol., February 1, 2005; 174(3): 1205 - 1212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Roth, C. Sustmann, M. Kieslinger, A. Gilmozzi, D. Irmer, E. Kremmer, C. Turck, and R. Grosschedl PIASy-Deficient Mice Display Modest Defects in IFN and Wnt Signaling J. Immunol., November 15, 2004; 173(10): 6189 - 6199. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. L.J.M. Zeeuwen, I. M.J.J. van Vlijmen-Willems, D. Olthuis, H. T. Johansen, K. Hitomi, I. Hara-Nishimura, J. C. Powers, K. E. James, H. J. op den Camp, R. Lemmens, et al. Evidence that unrestricted legumain activity is involved in disturbed epidermal cornification in cystatin M/E deficient mice Hum. Mol. Genet., May 15, 2004; 13(10): 1069 - 1079. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Buhling, N. Waldburg, A. Reisenauer, A. Heimburg, H. Golpon, and T. Welte Lysosomal cysteine proteases in the lung: role in protein processing and immunoregulation Eur. Respir. J., April 1, 2004; 23(4): 620 - 628. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zheng, P. M. Chou, B. L. Mirkin, and A. Rebbaa Senescence-initiated Reversal of Drug Resistance: Specific Role of Cathepsin L Cancer Res., March 1, 2004; 64(5): 1773 - 1780. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Anway, W. W. Wright, B. R. Zirkin, N. Korah, J. S. Mort, and L. Hermo Expression and Localization of Cathepsin K In Adult Rat Sertoli Cells Biol Reprod, March 1, 2004; 70(3): 562 - 569. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H. Ebert, S. A. Kopecky-Bromberg, and T. S. Dermody Cathepsin B Is Inhibited in Mutant Cells Selected during Persistent Reovirus Infection J. Biol. Chem., January 30, 2004; 279(5): 3837 - 3851. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Masumoto, Y. Sakata, K. Arima, I. Nakao, and K. Izuhara Inhibitory Mechanism of a Cross-class Serpin, the Squamous Cell Carcinoma Antigen 1 J. Biol. Chem., November 14, 2003; 278(46): 45296 - 45304. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Huang, A. Vaag, E. Carlsson, M. Hansson, B. Ahren, and L. Groop Impaired Cathepsin L Gene Expression in Skeletal Muscle Is Associated With Type 2 Diabetes Diabetes, September 1, 2003; 52(9): 2411 - 2418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Boya, K. Andreau, D. Poncet, N. Zamzami, J.-L. Perfettini, D. Metivier, D. M. Ojcius, M. Jaattela, and G. Kroemer Lysosomal Membrane Permeabilization Induces Cell Death in a Mitochondrion-dependent Fashion J. Exp. Med., May 19, 2003; 197(10): 1323 - 1334. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. W. Wright, L. Smith, C. Kerr, and M. Charron Mice That Express Enzymatically Inactive Cathepsin L Exhibit Abnormal Spermatogenesis Biol Reprod, February 1, 2003; 68(2): 680 - 687. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. L.J.M. Zeeuwen, I. M.J.J. van Vlijmen-Willems, W. Hendriks, G. F.M. Merkx, and J. Schalkwijk A null mutation in the cystatin M/E gene of ichq mice causes juvenile lethality and defects in epidermal cornification Hum. Mol. Genet., November 1, 2002; 11(23): 2867 - 2875. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H. Ebert, J. Deussing, C. Peters, and T. S. Dermody Cathepsin L and Cathepsin B Mediate Reovirus Disassembly in Murine Fibroblast Cells J. Biol. Chem., June 28, 2002; 277(27): 24609 - 24617. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Felbor, B. Kessler, W. Mothes, H. H. Goebel, H. L. Ploegh, R. T. Bronson, and B. R. Olsen Neuronal loss and brain atrophy in mice lacking cathepsins B and L PNAS, June 11, 2002; 99(12): 7883 - 7888. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Tobin, K. Foitzik, T. Reinheckel, L. Mecklenburg, V. A. Botchkarev, C. Peters, and R. Paus The Lysosomal Protease Cathepsin L Is an Important Regulator of Keratinocyte and Melanocyte Differentiation During Hair Follicle Morphogenesis and Cycling Am. J. Pathol., May 1, 2002; 160(5): 1807 - 1821. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Stypmann, K. Glaser, W. Roth, D. J. Tobin, I. Petermann, R. Matthias, G. Monnig, W. Haverkamp, G. Breithardt, W. Schmahl, et al. Dilated cardiomyopathy in mice deficient for the lysosomal cysteine peptidase cathepsin L PNAS, April 30, 2002; 99(9): 6234 - 6239. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. A. BOTCHKAREV, N. V. BOTCHKAREVA, M. NAKAMURA, O. HUBER, K. FUNA, R. LAUSTER, R. PAUS, and B. A. GILCHREST Noggin is required for induction of the hair follicle growth phase in postnatal skin FASEB J, October 1, 2001; 15(12): 2205 - 2214. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. S. Stenn and R. Paus Controls of Hair Follicle Cycling Physiol Rev, January 1, 2001; 81(1): 449 - 494. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Stypmann, K. Glaser, W. Roth, D. J. Tobin, I. Petermann, R. Matthias, G. Monnig, W. Haverkamp, G. Breithardt, W. Schmahl, et al. Dilated cardiomyopathy in mice deficient for the lysosomal cysteine peptidase cathepsin L PNAS, April 30, 2002; 99(9): 6234 - 6239. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
