Caspase-mediated cleavage of syntaxin 5 and giantin accompanies inhibition of secretory traffic during apoptosis

• Published in: Journal of cell science Vol. 117; no. 7; pp. 1139 - 1150
• Main Authors: Lowe, Martin, Lane, Jon D., Woodman, Philip G., Allan, Victoria J.
• Format: Journal Article
• Language: English
• Published: England 01.03.2004
• Subjects: Animals; Apoptosis - physiology; Biological Transport, Active; Caspase 3; Caspases - metabolism; Endoplasmic Reticulum - metabolism; Golgi Apparatus - metabolism; HeLa Cells; Humans; In Vitro Techniques; Membrane Proteins - chemistry; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mutagenesis, Site-Directed; Phenotype; Protein Structure, Tertiary; Qa-SNARE Proteins; Rats; Recombinant Proteins - chemistry; Recombinant Proteins - genetics; Recombinant Proteins - metabolism
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.00950

We report the caspase-dependent cleavage of two Golgi-associated transport factors during apoptosis. The tethering factor giantin is rapidly cleaved both in vitro and in vivo at a conserved site, to generate a stable membrane-anchored domain and a soluble domain that is subject to further caspase-dependent cleavage. The t-SNARE syntaxin 5 is also cleaved rapidly, resulting in the separation of the catalytic membrane-proximal domain from an N-terminal regulatory domain. Cleavage of giantin and syntaxin 5 is accompanied by a cessation of vesicular transport between the ER and the Golgi complex, which first manifests itself as a block in ER exit. The contribution that such an inhibition of trafficking may make towards the generation of an apoptotic phenotype is discussed.