JCB logo
Accuri Cytometers
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 22 November 2004. doi:10.1083/jcb.200406101
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 167, Number 4, 735-744
This Article
Right arrow Full Text
Right arrow PDF (Full Text)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
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 Siegel, R. M.
Right arrow Articles by Lenardo, M. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Siegel, R. M.
Right arrow Articles by Lenardo, M. J.
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?

Article

 SPOTS : signaling protein oligomeric transduction structures are early mediators of death receptor–induced apoptosis at the plasma membrane



Richard M. Siegel1,3, Jagan R. Muppidi3, Malabika Sarker1, Adrian Lobito3, Melinda Jen1, David Martin1, Stephen E. Straus2, and Michael J. Lenardo1

1 Laboratory of Immunology, National Institute of Allergy and Infectious Diseases
2 Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases
3 Immunoregulation Unit, Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MA 20892

Correspondence to Richard M. Siegel: rsiegel{at}nih.gov

Fas (CD95, APO-1, TNFRSF6) is a TNF receptor superfamily member that directly triggers apoptosis and contributes to the maintenance of lymphocyte homeostasis and prevention of autoimmunity. Although FADD and caspase-8 have been identified as key intracellular mediators of Fas signaling, it is not clear how recruitment of these proteins to the Fas death domain leads to activation of caspase-8 in the receptor signaling complex. We have used high-resolution confocal microscopy and live cell imaging to study the sequelae of early events in Fas signaling. These studies have revealed a new stage of Fas signaling in which receptor ligation leads to the formation of surface receptor oligomers that we term signaling protein oligomerization transduction structures (SPOTS). Formation of SPOTS depends on the presence of an intact Fas death domain and FADD but is independent of caspase activity. Analysis of cells expressing Fas mutations from patients with the autoimmune lymphoproliferative syndrome (ALPS) reveals that formation of SPOTS can be disrupted by distinct mechanisms in ALPS.

D. Martin's present address is Dept. of Medicine, University of Washington School of Medicine, Seattle, WA 98195.

Abbreviations used in this paper: ALPS, autoimmune lymphoproliferative syndrome; DD, death domain; DISC, death-inducing signaling complex; FasL, Fas ligand; SPOTS, signaling protein oligomerization transduction structures.


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