HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 35, 33194-33199, August 29, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/35/33194    most recent M302742200v1 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 Shirahama-Noda, K. Articles by Hara-Nishimura, I. Search for Related Content PubMed PubMed Citation Articles by Shirahama-Noda, K. Articles by Hara-Nishimura, I. Social Bookmarking                      What's this?

Biosynthetic Processing of Cathepsins and Lysosomal Degradation Are Abolished in Asparaginyl Endopeptidase-deficient Mice^*

Kanae Shirahama-Noda , Akitsugu Yamamoto  ¶, Kazushi Sugihara ||, Noriyoshi Hashimoto ||, Masahide Asano ||, Mikio Nishimura  and Ikuko Hara-Nishimura ** 

From the Department of Cell Biology, National Institute for Basic Biology, Okazaki 444-8585, Japan, Department of Physiology, Kansai Medical University, Moriguchi 570-8506, Japan, ^||Graduate School of Medical Science, Kanazawa University, Kanazawa 920-8640, Japan, and ^**Graduate School of Science, Kyoto University, Kitashirakawa, Sakyo-ku, Kyoto 606-8502, Japan

Asparaginyl endopeptidase (AEP)/legumain, an asparagine-specific cysteine proteinase in animals, is an ortholog of plant vacuolar processing enzyme (VPE), which processes the exposed asparagine residues of various vacuolar proteins. In search for its physiological role in mammals, here we generated and characterized AEP-deficient mice. Although their body weights were significantly reduced, they were normally born and fertile. In the wild-type kidney where the expression of AEP was exceedingly high among various organs, the localization of AEP was mainly found in the lamp-2-positive late endosomes in the apical region of the proximal tubule cells. In these cells of AEP-deficient mice, the lamp-2-positive membrane structures were found to be greatly enlarged. These aberrant lysosomes, merged with the late endosomes, accumulated electron-dense and membranous materials. Furthermore, the processing of the lysosomal proteases, cathepsins B, H, and L, from the single-chain forms into the two-chain forms was completely defected in the deficient mice. Thus, the AEP deficiency caused the accumulation of macromolecules in the lysosomes, highlighting a pivotal role of AEP in the endosomal/lysosomal degradation system.

Received for publication, March 18, 2003 , and in revised form, May 20, 2003.

^* This work has been supported in part by CREST of Japan Science and Technology Corporation and Grant-in-aid 12138205 for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ Present address: Nagahama Institute of Bio-Science and Technology, Nagahama 526-0829, Japan.

To whom correspondence should be addressed. Tel./Fax: 81-75-753-4142; E-mail: ihnishi{at}gr.bot.kyoto-u.ac.jp.

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

This article has been cited by other articles:

				C. M. Costantino, H. C. Hang, S. C. Kent, D. A. Hafler, and H. L. Ploegh Lysosomal Cysteine and Aspartic Proteases Are Heterogeneously Expressed and Act Redundantly to Initiate Human Invariant Chain Degradation J. Immunol., March 1, 2008; 180(5): 2876 - 2885. [Abstract] [Full Text] [PDF]

				S. Desmarais, W. C. Black, R. Oballa, S. Lamontagne, D. Riendeau, P. Tawa, L. T. Duong, M. Pickarski, and M. D. Percival Effect of Cathepsin K Inhibitor Basicity on in Vivo Off-Target Activities Mol. Pharmacol., January 1, 2008; 73(1): 147 - 156. [Abstract] [Full Text] [PDF]

				M. Rokushima, K. Omi, K. Imura, A. Araki, N. Furukawa, F. Itoh, M. Miyazaki, J. Yamamoto, M. Rokushima, M. Okada, et al. Toxicogenomics of Drug-Induced Hemolytic Anemia by Analyzing Gene Expression Profiles in the Spleen Toxicol. Sci., November 1, 2007; 100(1): 290 - 302. [Abstract] [Full Text] [PDF]

				M. Papaspyridonos, A. Smith, K. G. Burnand, P. Taylor, S. Padayachee, K. E. Suckling, C. H. James, D. R. Greaves, and L. Patel Novel Candidate Genes in Unstable Areas of Human Atherosclerotic Plaques Arterioscler. Thromb. Vasc. Biol., August 1, 2006; 26(8): 1837 - 1844. [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]

				R. M Nepal, S. Mampe, B. Shaffer, A. H Erickson, and P. Bryant Cathepsin L maturation and activity is impaired in macrophages harboring M. avium and M. tuberculosis Int. Immunol., June 1, 2006; 18(6): 931 - 939. [Abstract] [Full Text] [PDF]

				S. Komiya, M. Shimizu, J. Ikenouchi, S. Yonemura, T. Matsui, Y. Fukunaga, H. Liu, F. Endo, S. Tsukita, and A. Nagafuchi Apical membrane and junctional complex formation during simple epithelial cell differentiation of F9 cells Genes Cells, November 1, 2005; 10(11): 1065 - 1080. [Abstract] [Full Text] [PDF]

				M. Kuroyanagi, K. Yamada, N. Hatsugai, M. Kondo, M. Nishimura, and I. Hara-Nishimura Vacuolar Processing Enzyme Is Essential for Mycotoxin-induced Cell Death in Arabidopsis thaliana J. Biol. Chem., September 23, 2005; 280(38): 32914 - 32920. [Abstract] [Full Text] [PDF]

				R. Richter, R. Bistrian, S. Escher, W.-G. Forssmann, J. Vakili, R. Henschler, N. Spodsberg, A. Frimpong-Boateng, and U. Forssmann Quantum Proteolytic Activation of Chemokine CCL15 by Neutrophil Granulocytes Modulates Mononuclear Cell Adhesiveness J. Immunol., August 1, 2005; 175(3): 1599 - 1608. [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. Nakaune, K. Yamada, M. Kondo, T. Kato, S. Tabata, M. Nishimura, and I. Hara-Nishimura A Vacuolar Processing Enzyme, {delta}VPE, Is Involved in Seed Coat Formation at the Early Stage of Seed Development PLANT CELL, March 1, 2005; 17(3): 876 - 887. [Abstract] [Full Text] [PDF]

				N. Hatsugai, M. Kuroyanagi, K. Yamada, T. Meshi, S. Tsuda, M. Kondo, M. Nishimura, and I. Hara-Nishimura A Plant Vacuolar Protease, VPE, Mediates Virus-Induced Hypersensitive Cell Death Science, August 6, 2004; 305(5685): 855 - 858. [Abstract] [Full Text] [PDF]

				K. Theilgaard-Monch, S. Knudsen, P. Follin, and N. Borregaard The Transcriptional Activation Program of Human Neutrophils in Skin Lesions Supports Their Important Role in Wound Healing J. Immunol., June 15, 2004; 172(12): 7684 - 7693. [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]

				T. Shimada, K. Yamada, M. Kataoka, S. Nakaune, Y. Koumoto, M. Kuroyanagi, S. Tabata, T. Kato, K. Shinozaki, M. Seki, et al. Vacuolar Processing Enzymes Are Essential for Proper Processing of Seed Storage Proteins in Arabidopsis thaliana J. Biol. Chem., August 22, 2003; 278(34): 32292 - 32299. [Abstract] [Full Text] [PDF]