Protein kinase d regulates trafficking of dendritic membrane proteins in developing neurons.
Protein kinase d regulates trafficking of dendritic membrane proteins in developing neurons.
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DOI：
10.1523/jneurosci.1879-08.2008
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发表时间：
2008-09-10
期刊：
影响因子：
--
通讯作者：
Cáceres A
中科院分区：
文献类型：
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作者：
Bisbal M;Conde C;Donoso M;Bollati F;Sesma J;Quiroga S;Díaz Añel A;Malhotra V;Marzolo MP;Cáceres A
在非神经元细胞中，蛋白激酶D（PKD）的失活会阻断高尔基体反面网状结构（TGN）运输载体的分裂，导致出现充满货物的长管。我们现在报道PKD1在神经元蛋白质运输中的功能。在培养的海马锥体细胞中，转铁蛋白受体（TfR）和低密度受体相关蛋白（LRP）主要被运输到树突，而不进入轴突。表达无激酶活性的PKD1或通过RNAi处理使其缺失，会显著且选择性地改变含有TfR和LRP的囊泡的细胞内运输和膜递送，而不会抑制从TGN的出芽或诱导高尔基体管状化。在PKD1被抑制后，树突膜蛋白被错误包装到运输VAMP2的载体中；这些囊泡分布到轴突和树突，但会从树突快速内吞，并优先递送到轴突膜。一种缺乏结合二酰甘油能力因而不能定位在高尔基体的PKD1激酶缺陷突变体不会导致TfR或LRP的错误分选。这些结果表明，在神经元中PKD1调节源自TGN的树突蛋白的分选，因此在神经元极性中起作用。
In non-neuronal cells inactivation of Protein Kinase D (PKD) blocks fission of TGN transport carriers inducing the appearance of long tubules filled with cargo. We now report on the function of PKD1 in neuronal protein trafficking. In cultured hippocampal pyramidal cells the transferrin receptor (TfR) and the low-density receptor-related protein (LRP) are predominantly transported to dendrites and excluded from axons. Expression of kinase-inactive PKD1 or its depletion by RNAi treatment dramatically and selectively alter the intracellular trafficking and membrane delivery of TfR and LRP-containing vesicles, without inhibiting exit from the TGN or inducing Golgi tubulation. After PKD1 suppression, dendritic membrane proteins are mispackaged into carriers that transport VAMP2; these vesicles distributed to both axons and dendrites, but are rapidly endocytosed from dendrites and preferentially delivered to the axonal membrane. A kinase defective mutant of PKD1 lacking the ability to bind dyacylglycerol and hence its Golgi localization does not cause missorting of TfR or LRP. These results suggest that in neurons PKD1 regulates TGN-derived sorting of dendritic proteins and hence has a role in neuronal polarity.