Gimap4 accelerates T-cell death.
Gimap4, a member of the newly identified GTPase of the immunity-associated protein family (Gimap), is strongly induced by the pre-T-cell receptor in precursor T lymphocytes, transiently shut off in double-positive thymocytes, and reappears after TCR-mediated positive selection. Here, we show that Gimap4 remains expressed constitutively in the cytosol of mature T cells. A C-terminal IQ domain binds calmodulin in the absence of calcium, and conserved PKC phosphorylation motifs are targets of concanavalin A (ConA)- or PMA/ionomycin-induced PKC activation. To address the role of Gimap4 in T-cell physiology, we completed the genomic organization of the gimap4 locus and generated a Gimap4-null mutant mouse. Studies in these mice revealed no critical role of Gimap4 in T-cell development but in the regulation of apoptosis. We have found that Gimap4 accelerates the execution of programmed cell death induced by intrinsic stimuli downstream of caspase-3 activation and phosphatidylserine exposure. Apoptosis directly correlates with the phosphorylation status of Gimap4.
Division of Immunology, The Netherlands Cancer Institute, Amsterdam.
Silke
S
Schnell
Corinne
C
Démollière
Paul
P
van den Berk
Heinz
H
Jacobs
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D003600:Cytosol / Q000737:chemistry; D020558:GTP Phosphohydrolases / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D019204:GTP-Binding Proteins; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010718:Phosphatidylserines / Q000378:metabolism; D010766:Phosphorylation; D013601:T-Lymphocytes / Q000166:cytology*
D051017:Apoptosis Regulatory Proteins; C400051:Ian1 protein, mouse; D010718:Phosphatidylserines; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins