Protection from endogenous perforin: glycans and the C terminus regulate exocytic trafficking in cytotoxic lymphocytes - PubMed (original) (raw)
. 2011 Jun 24;34(6):879-92.
doi: 10.1016/j.immuni.2011.04.007. Epub 2011 Jun 9.
Jenny Chia, Kylie A Browne, Annette Ciccone, Sarah Ellis, Jamie A Lopez, Olivia Susanto, Sandra Verschoor, Hideo Yagita, James C Whisstock, Joseph A Trapani, Ilia Voskoboinik
Affiliations
- PMID: 21658975
- DOI: 10.1016/j.immuni.2011.04.007
Free article
Protection from endogenous perforin: glycans and the C terminus regulate exocytic trafficking in cytotoxic lymphocytes
Amelia J Brennan et al. Immunity. 2011.
Free article
Abstract
Cytotoxic lymphocyte-mediated apoptosis is dependent on the delivery of perforin to secretory granules and its ability to form calcium-dependent pores in the target cell after granule exocytosis. It is unclear how cytotoxic lymphocytes synthesize and store perforin without incurring damage or death. We discovered that the extreme C terminus of perforin was essential for rapid trafficking from the endoplasmic reticulum to the Golgi compartment. Substitution of the C-terminal tryptophan residue resulted in retention of perforin in the ER followed by calcium-dependent toxic activity that eliminated host cells. We also found that N-linked glycosylation of perforin was critical for transport from the Golgi to secretory granules. Overall, an intact C terminus and N-linked glycosylation provide accurate and efficient export of perforin from the endoplasmic reticulum to the secretory granules and are critical for cytotoxic lymphocyte survival.
Copyright © 2011 Elsevier Inc. All rights reserved.
Comment in
- Intracellular trafficking of perforin: to thwart a killer.
Froelich C, Metkar S. Froelich C, et al. Immunity. 2011 Jun 24;34(6):823-5. doi: 10.1016/j.immuni.2011.06.008. Immunity. 2011. PMID: 21703535 Free PMC article.
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