A cascade of protein kinase C isozymes promotes cytoskeletal polarization in T cells.
A cascade of protein kinase C isozymes promotes cytoskeletal polarization in T cells.
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DOI：
10.1038/ni.2033
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发表时间：
2011-05-22
影响因子：
30.5
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中科院分区：
文献类型：
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T细胞微管组织中心（MTOC）向抗原呈递细胞的极化是由免疫突触（is）中二酰基甘油的积累驱动的。二酰基甘油与MTOC偶联的机制尚不清楚。利用T细胞受体的单细胞光激活，我们证明了三种不同的蛋白激酶C （PKC）异构体是由二酰基甘油分两个步骤招募到IS的。PKC-ε和PKC-η首先在较宽的膜区积累，PKC-θ则在较小的膜区积累。功能化实验表明，MTOC重定向需要PKC-θ， PKC-ε和PKC-η的冗余作用促进PKC-θ的聚集和随后的极化响应。这些结果确定了PKCs在T细胞极性中的先前未被描述的作用。
Polarization of the T cell microtubule-organizing center (MTOC) toward the antigen-presenting cell is driven by the accumulation of diacylglycerol at the immunological synapse (IS). The mechanisms that couple diacylglycerol to the MTOC are not known. Using single-cell photoactivation of the T cell receptor, we demonstrated that three distinct protein kinase C (PKC) isoforms are recruited by diacylglycerol to the IS in two steps. PKC-ε and PKC-η accumulated first in a broad region of membrane, while PKC-θ arrived later in a smaller zone. Functional experiments indicated that PKC-θ was required for MTOC reorientation, and that PKC-ε and PKC-η operated redundantly to promote PKC-θ recruitment and subsequent polarization responses. These results establish a previously uncharacterized role for PKCs in T cell polarity.