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© The Rockefeller University Press, 0021-9525/2003/1/153-a $5.00
The Journal of Cell Biology, Volume 160, Number 2, 153-a-153

Rejection and killing, without MPR

Cells lacking MPR still take up granzyme B.

Whether destroying a tumor or rejecting a transplanted organ, cytotoxic lymphocytes rely on proteases called granzymes to kill target cells, so the finding two years ago that the action of a granzyme requires the mannose-6-phosphate receptor (MPR) on a target cell raised hopes for developing new classes of anticancer and antirejection drugs. Now, on page 223, Trapani et al. demonstrate that this optimism was premature, since endocytosis through MPR is actually not required for granzyme-mediated cell killing in a variety of systems.Seeking to extend previous work (Motyka et al., 2000. Cell. 103:491–500), the authors first used cells defective for dynamin-mediated endocytosis or lacking MPR to study the uptake and effect of granzyme B, the major cell-killing granzyme. In cells unable to endocytose MPR, granzyme B uptake still occurs, albeit at a reduced rate, and cell killing is only slightly decreased. In mouse models, alloreactive tumor cells grafted under the renal capsule are rejected whether or not the cells can internalize MPR. The data suggest that when MPR-mediated uptake is blocked, granzyme B can still kill by entering cells through fluid phase endocytosis.

Alan W. Dove

alanwdove{at}earthlink.net

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A clathrin/dynamin- and mannose-6-phosphate receptor–independent pathway for granzyme B–induced cell death

Joseph A. Trapani, Vivien R. Sutton, Kevin Y.T. Thia, Yu Qin Li, Christopher J. Froelich, David A. Jans, Mauro S. Sandrin, and Kylie A. Browne
J. Cell Biol. 2003 160: 223-233. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 425K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Dove, A. W. Search for Related Content PubMed Articles by Dove, A. W. Related Collections Related Article Social Bookmarking                            What's this?