Protection from Endogenous Perforin: Glycans and the C Terminus Regulate Exocytic Trafficking in Cytotoxic Lymphocytes

作者：Brennan Amelia J; Chia Jenny; Browne Kylie A; Ciccone Annette; Ellis Sarah; Lopez Jamie A; Susanto Olivia; Verschoor Sandra; Yagita Hideo; Whisstock James C; Trapani Joseph A; Voskoboinik Ilia^*

来源：Immunity, 2011, 34(6): 879-892.

DOI：10.1016/j.immuni.2011.04.007

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.

• 出版日期2011-6-24