Granzyme B is recovered by natural killer cells via clathrin-dependent endocytosis.
When they recognize a target cell, natural killer (NK) cells mount an attack to kill the target by exerting their cytotoxicity via the exocytosis of cytotoxic granules. Although the details of this process (which includes the movement of cytotoxic granules in the immune synapse and their fusion with the plasma membrane, releasing granzymes and perforin into the synaptic cleft) are relatively better understood, the post-exocytosis regulation of the process is still largely unknown. Here we show that a clathrin-dependent endocytosis stimulated by target cell occurs in NK92 cell line, which is closely correlated with granzyme B recovery. Inhibition of the endocytosis significantly attenuates the cytotoxicity of NK92 cells. The NK cell recovery of its released effector molecules, in turn, suggests that endocytosis may well play a key role in the post exocytosis regulation of immune cells.
Li
Pan
P
Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Zheng
Guoying
G
Yang
Yan
Y
Zhang
Chunguang
C
Xiong
Ping
P
Xu
Yong
Y
Fang
Min
M
Tan
Zheng
Z
Zheng
Fang
F
Gong
Feili
F
D045744:Cell Line, Tumor; D002966:Clathrin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004705:Endocytosis / Q000276:immunology*; D053804:Granzymes / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*
D002966:Clathrin; D053804:Granzymes
Nat Rev Mol Cell Biol. 2007 Aug;8(8):603-12
17609668
Nature. 1994 Oct 6;371(6497):513-5
7935764
Cell. 2000 Oct 27;103(3):491-500
11081635
J Neurosci. 2007 Dec 12;27(50):13691-700
18077680
Curr Opin Immunol. 2003 Oct;15(5):516-21
14499259
J Biol Chem. 1985 Mar 25;260(6):3440-50
3838314
PLoS Biol. 2006 Jan;4(1):e9
16366734
Mol Immunol. 2005 Feb;42(4):501-10
15607806
Nat Neurosci. 2008 Jan;11(1):45-53
18066059
Traffic. 2008 Jun;9(6):1019-34
18363778
Cell Death Differ. 2008 Feb;15(2):251-62
17975553
Curr Opin Cell Biol. 2008 Oct;20(5):597-605
18639449
J Biol Chem. 2007 Sep 14;282(37):27503-27517
17644515
Semin Immunol. 2005 Feb;17(1):87-94
15582491
Nat Rev Immunol. 2008 Sep;8(9):713-25
19172692
Proc Natl Acad Sci U S A. 2005 Jan 4;102(1):123-7
15618404
Immunity. 2005 Sep;23(3):249-62
16169498
J Exp Med. 2002 Aug 19;196(4):493-503
12186841
Cell. 2008 Aug 22;134(4):657-67
18724938
Nature. 1998 Sep 3;395(6697):82-6
9738502
Biochem J. 2004 Jan 1;377(Pt 1):1-16
14505490
Biophys J. 1997 Jul;73(1):532-45
9199815
Annu Rev Immunol. 2008;26:389-420
18304003
J Biol Chem. 1996 Nov 1;271(44):27802-9
8910377
J Biol Chem. 2003 Jan 3;278(1):585-90
12411431
Nat Rev Mol Cell Biol. 2002 Feb;3(2):122-31
11836514
Immunol Rev. 2002 Nov;189:152-60
12445272
J Biol Chem. 2006 Oct 13;281(41):30485-91
16914553
Xenotransplantation. 2009 Jan-Feb;16(1):19-26
19243557
Cytometry. 2000 Dec 1;41(4):289-97
11084614
Science. 1999 Jul 9;285(5425):221-7
10398592
Clin Exp Immunol. 1995 Apr;100(1):164-72
7697916
Curr Opin Immunol. 2007 Jun;19(3):348-53
17433652