Inactivation of ceramide transfer protein during pro-apoptotic stress by Golgi disassembly and caspase cleavage

Suchismita Chandran, Carolyn E Machamer

Research output: Contribution to journalArticle

Abstract

The mammalian Golgi apparatus is composed of multiple stacks of cisternal membranes organized laterally into a polarized ribbon. Furthermore, trans-Golgi membranes come in close apposition with ER (endoplasmic reticulum) membranes to form ER-trans-Golgi contact sites, which may facilitate transfer of newly synthesized ceramide from the ER to SM (sphingomyelin) synthase at the trans-Golgi via CERT (ceramide transfer protein). CERT interacts with both ER and Golgi membranes, and together with Golgi morphology contributes to efficient SM synthesis. In the present study, we show that Golgi disassembly during proapoptotic stress induced by TNFα (tumour necrosis factor α) and anisomycin results in decreased levels of CERT at the Golgi region. This is accompanied by a caspase-dependent loss of full-length CERT and reduction in de novo SM synthesis. In vitro, CERT is cleaved by caspases 2, 3 and 9. Truncated versions of CERT corresponding to fragments generated by caspase 2 cleavage at Asp213 were mislocalized and did not promote efficient de novo SM synthesis. Thus it is likely that during cellular stress, disassembly of Golgi structure together with inactivation of CERT by caspases causes a reduction in ceramide trafficking and SM synthesis, and could contribute to the cellular response to proapoptotic stress.

Original languageEnglish (US)
Pages (from-to)391-401
Number of pages11
JournalBiochemical Journal
Volume442
Issue number2
DOIs
Publication statusPublished - Mar 1 2012

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Keywords

  • Apoptosis
  • Caspase
  • Ceramide transfer protein (CERT)
  • Golgi complex
  • Sphingomyelin synthesis

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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