Regulation of T cell survival through coronin-1-mediated generation of inositol-1,4,5-trisphosphate and calcium mobilization after T cell receptor triggering.
T cell homeostasis is essential for the functioning of the vertebrate immune system, but the intracellular signals required for T cell homeostasis are largely unknown. We here report that the WD-repeat protein family member coronin-1, encoded by the gene Coro1a, is essential in the mouse for T cell survival through its promotion of Ca2+ mobilization from intracellular stores. Upon T cell receptor triggering, coronin-1 was essential for the generation of inositol-1,4,5-trisphosphate from phosphatidylinositol-4,5-bisphosphate. The absence of coronin-1, although it did not affect T cell development, resulted in a profound defect in Ca2+ mobilization, interleukin-2 production, T cell proliferation and T cell survival. We conclude that coronin-1, through activation of Ca2+ release from intracellular stores, is an essential regulator of peripheral lymphocyte survival.
Mueller
Philipp
P
Biozentrum, University of Basel, Klingelbergstrasse 50-70, CH 4056 Basel, Switzerland.
Massner
Jan
J
Jayachandran
Rajesh
R
Combaluzier
Benoit
B
Albrecht
Imke
I
Gatfield
John
J
Blum
Carmen
C
Ceredig
Rod
R
Rodewald
Hans-Reimer
HR
Rolink
Antonius G
AG
Pieters
Jean
J
D000199:Actins / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000235:genetics / Q000502:physiology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis*; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism* / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
D000199:Actins; D008840:Microfilament Proteins; D011948:Receptors, Antigen, T-Cell; C072061:coronin proteins; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D002118:Calcium