QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online February 6, 2008
doi: 10.1242/10.1242/jcs.015255

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted 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 Spasic, D. Articles by Annaert, W. Search for Related Content PubMed PubMed Citation Articles by Spasic, D. Articles by Annaert, W. Social Bookmarking                         What's this?

Building -secretase – the bits and pieces

Laboratory for Membrane Trafficking, Center for Human Genetics (KULeuven) and Department of Molecular and Developmental Genetics (VIB), O&N1, Rm. 9.696, Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium

^* Author for correspondence (e-mail: Willem.Annaert{at}med.kuleuven.be)

Accepted 13 December 2007

-Secretase is a promiscuous aspartyl protease responsible for the final intramembrane cleavage of various type I transmembrane proteins after their large ectodomains are shed. The vast functional diversity of its substrates, which are involved in cell fate decisions, adhesion, neurite outgrowth and synapse formation, highlights the important role -secretase plays in development and neurogenesis. The most renowned substrates are the amyloid precursor protein and Notch, from which -secretase liberates amyloid β peptides and induces downstream signalling, respectively. -Secretase is a multiprotein complex containing presenilin (which harbours the catalytic site), nicastrin, APH1 and PEN2. Its assembly occurs under tight control of ER-Golgi recycling regulators, which allows defined quantities of complexes to reach post-Golgi compartments, where -secretase activity is regulated by multiple other factors. 3D-EM rendering reveals a complex with a translucent inner space, suggesting the presence of a water-filled cavity required for intramembrane proteolysis. Despite huge efforts, we are now only beginning to unravel the assembly, stoichiometry, activation and subcellular location of -secretase.

Key words: ER-Golgi transport, Gamma-secretase, Intramembrane proteolysis

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

This article has been cited by other articles:

				E. Area-Gomez, A. J.C. de Groof, I. Boldogh, T. D. Bird, G. E. Gibson, C. M. Koehler, W. H. Yu, K. E. Duff, M. P. Yaffe, L. A. Pon, et al. Presenilins Are Enriched in Endoplasmic Reticulum Membranes Associated with Mitochondria Am. J. Pathol., November 1, 2009; 175(5): 1810 - 1816. [Abstract] [Full Text] [PDF]

				I. Hayashi, S. Takatori, Y. Urano, H. Iwanari, N. Isoo, S. Osawa, M. A. Fukuda, T. Kodama, T. Hamakubo, T. Li, et al. Single Chain Variable Fragment against Nicastrin Inhibits the {gamma}-Secretase Activity J. Biol. Chem., October 9, 2009; 284(41): 27838 - 27847. [Abstract] [Full Text] [PDF]

				R. Pardossi-Piquard, S.-P. Yang, S. Kanemoto, Y. Gu, F. Chen, C. Bohm, J. Sevalle, T. Li, P. C. Wong, F. Checler, et al. APH1 Polar Transmembrane Residues Regulate the Assembly and Activity of Presenilin Complexes J. Biol. Chem., June 12, 2009; 284(24): 16298 - 16307. [Abstract] [Full Text] [PDF]

				I. Y. Tamboli, K. Prager, D. R. Thal, K. M. Thelen, I. Dewachter, C. U. Pietrzik, P. St. George-Hyslop, S. S. Sisodia, B. De Strooper, M. T. Heneka, et al. Loss of {gamma}-Secretase Function Impairs Endocytosis of Lipoprotein Particles and Membrane Cholesterol Homeostasis J. Neurosci., November 12, 2008; 28(46): 12097 - 12106. [Abstract] [Full Text] [PDF]

				A. Kiss, R. B. Troyanovsky, and S. M. Troyanovsky p120-Catenin Is a Key Component of the Cadherin-{gamma}-Secretase Supercomplex Mol. Biol. Cell, October 1, 2008; 19(10): 4042 - 4050. [Abstract] [Full Text] [PDF]