| First Author | Brennan AJ | Year | 2011 |
| Journal | Immunity | Volume | 34 |
| Issue | 6 | Pages | 879-92 |
| PubMed ID | 21658975 | Mgi Jnum | J:174008 |
| Mgi Id | MGI:5050774 | Doi | 10.1016/j.immuni.2011.04.007 |
| Citation | Brennan AJ, et al. (2011) Protection from endogenous perforin: glycans and the C terminus regulate exocytic trafficking in cytotoxic lymphocytes. Immunity 34(6):879-92 |
| abstractText | 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. |
