http://www.cnr.it/ontology/cnr/individuo/prodotto/ID38765

Syntaxin 4 is required for acid sphingomyelinase activity and apoptotic function. (Articolo in rivista)

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Syntaxin 4 is required for acid sphingomyelinase activity and apoptotic function. (Articolo in rivista) (literal)

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Cristiana Perrotta?, Laura Bizzozero?, Denise Cazzato§, Sara Morlacchi?, Emma Assi?, Fabio Simbari¶1, Yang Zhang , Erich Gulbins , Maria Teresa Bassi§, Patrizia Rosa**, and Emilio Clementi (2010)
Syntaxin 4 is required for acid sphingomyelinase activity and apoptotic function.
in Journal of biological chemistry (Online)
(literal)

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Cristiana Perrotta?, Laura Bizzozero?, Denise Cazzato§, Sara Morlacchi?, Emma Assi?, Fabio Simbari¶1, Yang Zhang , Erich Gulbins , Maria Teresa Bassi§, Patrizia Rosa**, and Emilio Clementi (literal)

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?Unit of Clinical Pharmacology, Department of Clinical Sciences, University Hospital \"Luigi Sacco,\" Universita` degli Studi di Milano, 20157 Milan, Italy, the §E. Medea Scientific Institute, 23842 Bosisio Parini, Lecco, Italy, the ¶Department of Biomedicinal Chemistry, Institute for Advanced Chemistry of Catalonia (CSIC), Jordi Girona 18-26, Barcelona, Spain, the Department of Molecular Biology and Center for Medical Biology, University of Duisburg-Essen, 45122 Essen, Germany, and the **Consiglio Nazionale delle Ricerche Institute of Neuroscience, Department of Medical Pharmacology, 20129 Milano, Italy (literal)

Titolo

Syntaxin 4 is required for acid sphingomyelinase activity and apoptotic function. (literal)

Abstract

Acid sphingomyelinase (A-SMase) is an important enzyme in sphingolipid metabolism and plays key roles in apoptosis, immunity, development, and cancer. In addition, it mediates cytotoxicity of cisplatin and some other chemotherapeutic drugs. The mechanism of A-SMase activation is still undefined. We now demonstrate that, upon CD95 stimulation, A-SMase is activated through translocation from intracellular compartments to the plasma membrane in an exocytic pathway requiring the t-SNARE protein syntaxin 4. Indeed, down-regulation of syntaxin 4 inhibits A-SMase translocation and activation induced by CD95 stimulation. This leads to inhibition of the CD95-triggered signaling events, including caspase 3 and 9 activation and apoptosis, activation of the survival pathway involving the protein kinase Akt, and important changes in cell cycle and proliferation. The molecular interaction between A-SMase and syntaxin 4 was not known and clarifies the mechanism of A-SMase activation. The novel actions of syntaxin 4 in sphingolipid metabolism and exocytosis we describe here define signaling mechanisms of broad relevance in cell pathophysiology. (literal)

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