Perforin activity at membranes leads to invaginations and vesicle formation
Praper, Tilen (Author), Kladnik, Aleš (Author), Anderluh, Gregor (Author)

URLURL - Presentation file, Visit http://dx.doi.org/10.1073/pnas.1107473108 This link opens in a new window

The cytotoxic cell granule secretory pathway is essential for immune defence. How the pore-forming protein perforin (PFN) facilitates the cytosolic delivery of granule-associated proteases (granzymes) remains enigmatic. Here we show that PFN is able to induce invaginations and formation of complete internal vesicles in giant unilamellar vesicles. Formation of internal vesicles depends on native PFN and calcium and antibody labeling shows the localization of PFN at the invaginations. This vesiculation is recapitulated in large unilamellar vesicles and in this case PFN oligomers can be seen associated with the necks of the invaginations. Capacitance measurements show PFN is able to increase a planar lipid membrane surface area in the absence of pore formation, in agreement with the ability to induce invaginations. Finally, addition of PFN to Jurkat cells causes the formation of internal vesicles prior to pore formation. PFN is capable of triggering an endocytosis-like event in addition to pore formation, suggesting a new paradigm for its role in delivering apoptosis-inducing granzymes into target cells.

Keywords:perforin, mambranes (biology), vesicles
Work type:Not categorized (r6)
Tipology:1.01 - Original Scientific Article
Organization:BF - Biotechnical Faculty
Number of pages:str. 21016-21021
Numbering:Vol. 108, no. 52
ISSN on article:0027-8424
DOI:10.1073/pnas.1107473108 Link is opened in a new window
COBISS.SI-ID:2493519 Link is opened in a new window
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Record is a part of a journal

Title:Proceedings of the National Academy of Sciences of the United States of America
Shortened title:Proc. Natl. Acad. Sci. U. S. A.
Publisher:National Academy of Sciences
COBISS.SI-ID:286487 This link opens in a new window

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