Dynamic recruitment of phospholipase C gamma at transiently immobilized GPI-anchored receptor clusters induces IP3-Ca2+ signaling: single-molecule tracking study 2.

Dynamic recruitment of phospholipase C gamma at transiently immobilized GPI-anchored receptor clusters induces IP3-Ca2+ signaling: single-molecule tracking study 2.
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DOI:
10.1083/jcb.200609175
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发表时间:
2007-05-21
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Kusumi A
Kusumi A
中科院分区:
其他
文献类型:
--
作者:
Suzuki KG;Fujiwara TK;Edidin M;Kusumi A

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CD 59簇是一种糖基磷脂酰肌醇锚定受体(GPI-AR),其生理大小约为6个CD 59分子,通过蛋白质-蛋白质和筏相互作用招募Gαi2和林恩。林恩可能被Gαi2结合在相同的CD 59簇中激活,诱导CD 59簇与F-肌动蛋白结合,导致其固定,称为刺激诱导的侧向扩散暂时停滞(STALL;寿命为0.57 s,大约每2 s发生一次)。GFP-PLCγ2和CD 59簇的同时单分子追踪显示,PLCγ2分子仅在经历STALL的CD 59簇处从细胞质瞬时(中值= 0.25 s)募集,产生IP 3-Ca 2+信号。因此,我们认为STALL中的CD 59簇可能是通过PLCγ2募集将细胞外GPI-AR信号转导为细胞内IP 3-Ca 2+信号的关键(尽管是短暂的)平台。持续数分钟以上的长时间模拟大量IP 3-Ca 2+信号可能是由短暂的数字样IP 3爆发的总和产生的,每个爆发都是由PLCγ2分子短暂募集到STALLed CD 59产生的。
Clusters of CD59, a glycosylphosphatidylinositol-anchored receptor (GPI-AR), with physiological sizes of approximately six CD59 molecules, recruit Gαi2 and Lyn via protein–protein and raft interactions. Lyn is activated probably by the Gαi2 binding in the same CD59 cluster, inducing the CD59 cluster's binding to F-actin, resulting in its immobilization, termed stimulation-induced temporary arrest of lateral diffusion (STALL; with a 0.57-s lifetime, occurring approximately every 2 s). Simultaneous single-molecule tracking of GFP-PLCγ2 and CD59 clusters revealed that PLCγ2 molecules are transiently (median = 0.25 s) recruited from the cytoplasm exclusively at the CD59 clusters undergoing STALL, producing the IP3–Ca2+ signal. Therefore, we propose that the CD59 cluster in STALL may be a key, albeit transient, platform for transducing the extracellular GPI-AR signal to the intracellular IP3–Ca2+ signal, via PLCγ2 recruitment. The prolonged, analogue, bulk IP3–Ca2+ signal, which lasts for more than several minutes, is likely generated by the sum of the short-lived, digital-like IP3 bursts, each created by the transient recruitment of PLCγ2 molecules to STALLed CD59.
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