TY - JOUR
T1 - Cytotoxic cell granule-mediated apoptosis
T2 - Perforin delivers granzyme b-serglycin complexes into target cells without plasma membrane pore formation
AU - Metkar, Sunil S.
AU - Wang, Baikun
AU - Aguilar-Santelises, Miguel
AU - Raja, Srikumar M.
AU - Uhlin-Hansen, Lars
AU - Podack, Eckhard
AU - Trapani, Joseph A.
AU - Froelich, Christopher J.
PY - 2002/1/1
Y1 - 2002/1/1
N2 - The mechanism underlying perforin (PFN)-dependent delivery of apoptotic granzymes during cytotoxic cell granule-mediated death remains speculative. Granzyme B (GrB) and perforin were found to coexist as multimeric complexes with the proteoglycan serglycin (SG) in cytotoxic granules, and cytotoxic cells were observed to secrete exclusively macromolecular GrB-SG. Contrary to the view that PFN acts as a gateway for granzymes through the plasma membrane, monomeric PFN and, strikingly, PFN-SG complexes were shown to mediate cytosolic delivery of macromolecular GrB-SG without producing detectable plasma membrane pores. These results indicate that granule-mediated apoptosis represents a phenomenon whereby the target cell perceives granule contents as a multi meric complex consisting of SG, PFN, and granzymes, which are, respectively, the scaffold, translocator, and targeting/informational components of this modular delivery system.
AB - The mechanism underlying perforin (PFN)-dependent delivery of apoptotic granzymes during cytotoxic cell granule-mediated death remains speculative. Granzyme B (GrB) and perforin were found to coexist as multimeric complexes with the proteoglycan serglycin (SG) in cytotoxic granules, and cytotoxic cells were observed to secrete exclusively macromolecular GrB-SG. Contrary to the view that PFN acts as a gateway for granzymes through the plasma membrane, monomeric PFN and, strikingly, PFN-SG complexes were shown to mediate cytosolic delivery of macromolecular GrB-SG without producing detectable plasma membrane pores. These results indicate that granule-mediated apoptosis represents a phenomenon whereby the target cell perceives granule contents as a multi meric complex consisting of SG, PFN, and granzymes, which are, respectively, the scaffold, translocator, and targeting/informational components of this modular delivery system.
UR - http://www.scopus.com/inward/record.url?scp=0036195424&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036195424&partnerID=8YFLogxK
U2 - 10.1016/S1074-7613(02)00286-8
DO - 10.1016/S1074-7613(02)00286-8
M3 - Article
C2 - 11911826
AN - SCOPUS:0036195424
VL - 16
SP - 417
EP - 428
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 3
ER -