A role for talin in presynaptic function.

A role for talin in presynaptic function.
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DOI:
10.1083/jcb.200406020
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发表时间:
2004-10-11
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
De Camilli P
De Camilli P
中科院分区:
其他
文献类型:
--
作者:
Morgan JR;Di Paolo G;Werner H;Shchedrina VA;Pypaert M;Pieribone VA;De Camilli P

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Talin是整合素和细胞黏附部位的肌动蛋白细胞骨架之间的适配器,最近发现存在于神经元突触中,其功能尚不清楚。Talin与脑内主要的磷脂酰肌醇-(4)-二磷酸[PI(4,5)P2]合成酶--磷脂酰肌醇-(4)-磷酸5-激酶I型γ相互作用。为了深入了解talin的突触作用,我们向竞争talin-PIP激酶相互作用的大鳗类轴突试剂中进行了显微注射,然后检测了它们对突触结构的影响。观察到突触肌动蛋白的显著减少和网状蛋白介导的突触小泡内吞功能的损害。内吞缺陷包括在这些突触上扰乱肌动蛋白后观察到的宽颈笼状蛋白包裹的凹坑的堆积。因此,PIP激酶与突触前间隔中talin的相互作用提供了一种协调PI(4,5)P2合成、肌动蛋白动力学和内吞作用的机制,并进一步支持了肌动蛋白和网状蛋白介导的内吞作用之间的功能联系。
Talin, an adaptor between integrin and the actin cytoskeleton at sites of cell adhesion, was recently found to be present at neuronal synapses, where its function remains unknown. Talin interacts with phosphatidylinositol-(4)-phosphate 5-kinase type Iγ, the major phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2]–synthesizing enzyme in brain. To gain insight into the synaptic role of talin, we microinjected into the large lamprey axons reagents that compete the talin–PIP kinase interaction and then examined their effects on synaptic structure. A dramatic decrease of synaptic actin and an impairment of clathrin-mediated synaptic vesicle endocytosis were observed. The endocytic defect included an accumulation of clathrin-coated pits with wide necks, as previously observed after perturbing actin at these synapses. Thus, the interaction of PIP kinase with talin in presynaptic compartments provides a mechanism to coordinate PI(4,5)P2 synthesis, actin dynamics, and endocytosis, and further supports a functional link between actin and clathrin-mediated endocytosis.
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