Advertisement
JBC

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


     

Originally published In Press as doi:10.1074/jbc.M302742200 on May 29, 2003

J. Biol. Chem., Vol. 278, Issue 35, 33194-33199, August 29, 2003
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
278/35/33194    most recent
M302742200v1
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 Shirahama-Noda, K.
Right arrow Articles by Hara-Nishimura, I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shirahama-Noda, K.
Right arrow Articles by Hara-Nishimura, I.
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?

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

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

From the {ddagger}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.

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


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
 Proc. Natl. Acad. Sci. USAHome page
C.-B. Chan, M. Abe, N. Hashimoto, C. Hao, I. R. Williams, X. Liu, S. Nakao, A. Yamamoto, C. Zheng, J.-I. Henter, et al.
Mice lacking asparaginyl endopeptidase develop disorders resembling hemophagocytic syndrome
PNAS, January 13, 2009; 106(2): 468 - 473.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
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]

Home page
 Mol. Pharmacol.Home page
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]

Home page
 Toxicol SciHome page
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]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
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]

Home page
 J. Biol. Chem.Home page
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]

Home page
 Int ImmunolHome page
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]

Home page
 GENES CELLSHome page
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]

Home page
 J. Biol. Chem.Home page
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]

Home page
 J. Immunol.Home page
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]

Home page
 J. Immunol.Home page
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]

Home page
 Plant CellHome page
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]

Home page
 ScienceHome page
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]

Home page
 J. Immunol.Home page
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]

Home page
 Hum Mol GenetHome page
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]

Home page
 J. Biol. Chem.Home page
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]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2003 by the American Society for Biochemistry and Molecular Biology.
Advertisement
spacer
Advertisement
Advertisement