JCB logo
Accuri Cytometers
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 573K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wolins, N.
Right arrow Articles by Bonifacino, J. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wolins, N.
Right arrow Articles by Bonifacino, J. S.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

© The Rockefeller University Press, 0021-9525/1997//1735 $5.00
The Journal of Cell Biology, Volume 139, Number 7, , 1997 1735-1745

Article

Aggregation As a Determinant of Protein Fate in Post-Golgi Compartments: Role of the Luminal Domain of Furin in Lysosomal Targeting



Nathan Wolins, Herbert Bosshart, Helmut Küster, and Juan S. Bonifacino

Cell Biology and Metabolism Branch, National Institite of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892

The mammalian endopeptidase furin is a type 1 integral membrane protein that is predominantly localized to the TGN and is degraded in lysosomes with a t1/2 = 2–4 h. Whereas the localization of furin to the TGN is largely mediated by sorting signals in the cytosolic tail of the protein, we show here that targeting of furin to lysosomes is a function of the luminal domain of the protein. Inhibition of lysosomal degradation results in the accumulation of high molecular weight aggregates of furin; aggregation is also dependent on the luminal domain of furin. Temperature and pharmacologic manipulations suggest that furin aggregation occurs in the TGN and thus precedes delivery to lysosomes. These findings are consistent with a model in which furin becomes progressively aggregated in the TGN, an event that leads to its transport to lysosomes. Our observations indicate that changes in the aggregation state of luminal domains can be potent determinants of biosynthetic targeting to lysosomes and suggest the possible existence of quality control mechanisms for disposal of aggregated proteins in compartments of the secretory pathway other than the endoplasmic reticulum.

Abbreviations used in this paper: DTSSP, dithio bis-sulfosuccinimidylpropionate; HA, hemagglutinin epitope; MHC, major histocompatibility complex; RBL, rat basophilic leukemia; Tac, {alpha} chain of the interleukin-2 receptor.

Address all correspondence to J.S. Bonifacino, CBMB, NICHD, National Institutes of Health, Building 18T Room 101, 18 Library Drive, MSC 5430, Bethesda, MD 20892-5430. Tel.: (301) 496-6368. Fax: (301) 402-0078. E-mail: juan{at}helix.nih.gov

H. Bosshart's present address is LRF Virus Centre, University of Glasgow, Bearsden Road, Glasgow G61 1QH, United Kingdom.

H. Küster's present address is Ludwig-Maximilians-Universität, Pettenkoferstrasse 8a, 80336 München, Germany.


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 Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents