C2-domain mediated nano-cluster formation increases calcium signaling efficiency

被引:15
作者
Bonny, Mike [1 ]
Hui, Xin [2 ]
Schweizer, Julia [2 ]
Kaestner, Lars [2 ]
Zeug, Andre [3 ]
Kruse, Karsten [1 ,4 ,5 ]
Lipp, Peter [2 ]
机构
[1] Univ Saarland, Theoret Phys, Saarbrucken, Germany
[2] Univ Saarland, Inst Mol Cell Biol, Fac Med, Homburg, Germany
[3] Hannover Med Sch, Ctr Physiol, Cellular Neurophysiol, Hannover, Germany
[4] Univ Geneva, Dept Biochem, 30 Quai Ernest Ansermet, CH-1211 Geneva, Switzerland
[5] Univ Geneva, Dept Theoret Phys, 30 Quai Ernest Ansermet, CH-1211 Geneva, Switzerland
关键词
PROTEIN-KINASE-C; MEMBRANE-FUSION; PHOSPHORYLATION; SYNAPTOTAGMIN; ACTIVATION; DOMAIN; ALPHA; BETA; FRET; PKC;
D O I
10.1038/srep36028
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Conventional protein kinase Cs (cPKCs) are key signaling proteins for transducing intracellular Ca2+ signals into downstream phosphorylation events. However, the lifetime of individual membrane-bound activated cPKCs is an order of magnitude shorter than the average time needed for target-protein phosphorylation. Here, we employed intermolecular Forster resonance energy transfer (FRET) in living cells combined with computational analysis to study the spatial organization of cPKCs bound to the plasma membrane. We discovered Ca2+-dependent cPKC nano-clusters that significantly extend cPKC's plasma-membrane residence time. These protein patterns resulted from self-assembly mediated by Ca2+-binding C2-domains, which are widely used for membrane-targeting of Ca2+-sensing proteins. We also established clustering of other unrelated C2-domain containing proteins, suggesting that nano-cluster formation is a key step for efficient cellular Ca2+-signaling.
引用
收藏
页数:11
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