|
|
Blood, 15 February 2008, Vol. 111, No. 4, pp. 2290-2299.
Prepublished online as a Blood First Edition Paper on December 3, 2007; DOI 10.1182/blood-2007-06-096529.
 Previous Article | Table of Contents | Next Article 
NEOPLASIA
Semaphorin3A signaling controls Fas (CD95)-mediated apoptosis by promoting Fas translocation into lipid rafts
Simona Moretti1,2,
Antonio Procopio1,2,
Raffaella Lazzarini1,2,
Maria Rita Rippo1,2,
Roberto Testa3,
Maurizio Marra3,
Luca Tamagnone4, and
Alfonso Catalano1,2
1 Department of Molecular Pathology and Innovative Therapies, Polytechnic University of Marche, Ancona;
2 Center of Cytology and
3 Diabetology Unit, Research Department, Italian National Research Centers on Aging, Ancona; and
4 Institute for Cancer Research and Treatment, University of Turin, Candiolo, Italy
Semaphorins and their receptors (plexins) have pleiotropic biologic functions, including regulation of immune responses. However, the role of these molecules inside the immune system and the signal transduction mechanism(s) they use are largely unknown. Here, we show that Semaphorin3A (Sema3A) triggers a proapoptotic program that sensitizes leukemic T cells to Fas (CD95)-mediated apoptosis. We found that Sema3A stimulation provoked Fas translocation into lipid raft microdomains before binding with agonistic antibody or FasL (CD95L). Disruption of lipid rafts reduced sensitivity to Fas-mediated apoptosis in the presence of Sema3A. Furthermore, we show that plexin-A1, together with Sema3A-binding neuropilin-1, was rapidly incorporated into membrane rafts after ligand stimulation, resulting in the transport of actin-linking proteins into Fas-enriched rafts. Cells expressing a dominant-negative mutant of plexin-A1 did not show Fas clustering and apoptosis on Sema3A/Fas costimulation. This work identifies a novel biologic function of semaphorins and presents an unexpected signaling mechanism linking semaphorin to the tumor necrosis factor family receptors.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
C. Petrovas, B. Chaon, D. R. Ambrozak, D. A. Price, J. J. Melenhorst, B. J. Hill, C. Geldmacher, J. P. Casazza, P. K. Chattopadhyay, M. Roederer, et al.
Differential Association of Programmed Death-1 and CD57 with Ex Vivo Survival of CD8+ T Cells in HIV Infection
J. Immunol.,
July 15, 2009;
183(2):
1120 - 1132.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Capparuccia and L. Tamagnone
Semaphorin signaling in cancer cells and in cells of the tumor microenvironment - two sides of a coin
J. Cell Sci.,
June 1, 2009;
122(11):
1723 - 1736.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Catalano, R. Lazzarini, S. Di Nuzzo, S. Orciari, and A. Procopio
The Plexin-A1 Receptor Activates Vascular Endothelial Growth Factor-Receptor 2 and Nuclear Factor-{kappa}B to Mediate Survival and Anchorage-Independent Growth of Malignant Mesothelioma Cells
Cancer Res.,
February 15, 2009;
69(4):
1485 - 1493.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. C. Schecterson and M. Bothwell
An All-Purpose Tool for Axon Guidance
Sci. Signal.,
November 25, 2008;
1(47):
pe50 - pe50.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Salikhova, L. Wang, A. A. Lanahan, M. Liu, M. Simons, W. P. J. Leenders, D. Mukhopadhyay, and A. Horowitz
Vascular Endothelial Growth Factor and Semaphorin Induce Neuropilin-1 Endocytosis via Separate Pathways
Circ. Res.,
September 12, 2008;
103(6):
e71 - e79.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
