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 pro-apoptotic 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 pro-apoptotic stress.
Skip Nav Destination
Article navigation
March 2012
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
February 13 2012
Inactivation of ceramide transfer protein during pro-apoptotic stress by Golgi disassembly and caspase cleavage
Suchismita Chandran;
Suchismita Chandran
1Department of Cell Biology, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, U.S.A.
Search for other works by this author on:
Carolyn E. Machamer
Carolyn E. Machamer
1
1Department of Cell Biology, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, U.S.A.
1To whom correspondence should be addressed (email machamer@jhmi.edu).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
August 09 2011
Revision Received:
November 24 2011
Accepted:
December 01 2011
Accepted Manuscript online:
December 01 2011
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2012 Biochemical Society
2012
Biochem J (2012) 442 (2): 391–401.
Article history
Received:
August 09 2011
Revision Received:
November 24 2011
Accepted:
December 01 2011
Accepted Manuscript online:
December 01 2011
Citation
Suchismita Chandran, Carolyn E. Machamer; Inactivation of ceramide transfer protein during pro-apoptotic stress by Golgi disassembly and caspase cleavage. Biochem J 1 March 2012; 442 (2): 391–401. doi: https://doi.org/10.1042/BJ20111461
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.