The mammalian Golgi complex is comprised of a ribbon of stacked cisternal membranes often located in the pericentriolar region of the cell. Here, we report that during apoptosis the Golgi ribbon is fragmented into dispersed clusters of tubulo-vesicular membranes. We have found that fragmentation is caspase dependent and identified GRASP65 (Golgi reassembly and stacking protein of 65 kD) as a novel caspase substrate. GRASP65 is cleaved specifically by caspase-3 at conserved sites in its membrane distal COOH terminus at an early stage of the execution phase. Expression of a caspase-resistant form of GRASP65 partially preserved cisternal stacking and inhibited breakdown of the Golgi ribbon in apoptotic cells. Our results suggest that GRASP65 is an important structural component required for maintenance of Golgi apparatus integrity.
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4 February 2002
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January 28 2002
Caspase-mediated cleavage of the stacking protein GRASP65 is required for Golgi fragmentation during apoptosis
Jon D. Lane,
Jon D. Lane
1School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom
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John Lucocq,
John Lucocq
2School of Life Sciences, WTB/MSI Complex, University of Dundee, Dundee DD1 5EH, United Kingdom
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James Pryde,
James Pryde
3Department of Medical and Radiological Sciences, The University of Edinburgh, EH8 9YL Edinburgh, United Kingdom
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Francis A. Barr,
Francis A. Barr
4Max-Planck Institute of Biochemistry, Department of Cell Biology, D-82152 Martinsried, Germany
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Philip G. Woodman,
Philip G. Woodman
1School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom
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Victoria J. Allan,
Victoria J. Allan
1School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom
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Martin Lowe
Martin Lowe
1School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom
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Jon D. Lane
1School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom
John Lucocq
2School of Life Sciences, WTB/MSI Complex, University of Dundee, Dundee DD1 5EH, United Kingdom
James Pryde
3Department of Medical and Radiological Sciences, The University of Edinburgh, EH8 9YL Edinburgh, United Kingdom
Francis A. Barr
4Max-Planck Institute of Biochemistry, Department of Cell Biology, D-82152 Martinsried, Germany
Philip G. Woodman
1School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom
Victoria J. Allan
1School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom
Martin Lowe
1School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom
Address correspondence to Martin Lowe, School of Biological Sciences, University of Manchester, 2.205 Stopford Bldg., Oxford Rd., Manchester M13 9PT, U.K. Tel.: 44-161-275-5387. Fax: 44-161-275-5082. E-mail: [email protected]
The online version of this article contains supplemental material.
*
Abbreviation used in this paper: CDK, cyclin-dependent kinase.
Received:
October 02 2001
Revision Received:
December 13 2001
Accepted:
December 18 2001
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2002
J Cell Biol (2002) 156 (3): 495–509.
Article history
Received:
October 02 2001
Revision Received:
December 13 2001
Accepted:
December 18 2001
Citation
Jon D. Lane, John Lucocq, James Pryde, Francis A. Barr, Philip G. Woodman, Victoria J. Allan, Martin Lowe; Caspase-mediated cleavage of the stacking protein GRASP65 is required for Golgi fragmentation during apoptosis . J Cell Biol 4 February 2002; 156 (3): 495–509. doi: https://doi.org/10.1083/jcb.200110007
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