The cell cortex-localized protein CHDP-1 is required for dendritic development and transport in C. elegans neurons.
The cell cortex-localized protein CHDP-1 is required for dendritic development and transport in C. elegans neurons.
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DOI：
10.1371/journal.pgen.1010381
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发表时间：
2022-09
期刊：
影响因子：
4.5
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中科院分区：
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皮质肌动蛋白是细胞膜下的一层很薄的肌动蛋白网络，在细胞形态发生和迁移等许多过程中发挥着重要作用。神经元通常长出高度分枝的树突形态，这对神经回路组装至关重要。目前尚不清楚皮质肌动蛋白在树突中的组装是如何控制的，以及它对树突的发育、维持和功能是否起关键作用。在本研究中，我们发现线虫chdp-1基因的敲除导致幼虫阶段的树突形成缺陷和成虫的自发性树突退化。在chdp-1突变体中，树突状生长锥体中肌动蛋白的组装显著减少。PVD神经元感觉肌肉收缩，并充当本体感受器。Chdp-1的缺失使本体感觉丧失，而在PVD神经元中表达chdp-1可以挽救本体感觉。在高序分支中，chdp-1的缺失也严重影响了微管细胞骨架的组装、细胞内细胞器的运输和神经肽的分泌。有趣的是，SAX-1基因的敲除可以抑制chdp-1突变体的上述缺陷。SAX-1基因编码一个进化保守的丝氨酸/苏氨酸蛋白激酶。因此，我们的发现表明，CHDP-1和SAX-1在多树突状神经元中以相反的方式调节皮质肌动蛋白组装，这对树突的发育、维持和功能至关重要。神经元通常长出被称为“树突”的高度分枝的细胞突起，以接收来自环境或其他神经元的信号。在这些细胞内，有两种类型的细胞骨架，即肌动蛋白细胞骨架和微管细胞骨架，在树突状分支、生长和功能过程中发挥着重要作用。然而，神经元细胞骨架的动力学是如何控制的，目前还不完全清楚。以线虫(土壤中发现的一种微小蛔虫)为研究模型，我们发现CHDP-1是一种定位于细胞皮质的蛋白质，在树突中肌动蛋白和微管细胞骨架的形成中起着至关重要的作用。Chdp-1的突变导致树突状分支和细胞内细胞器运输的缺陷。Chdp-1突变体不能从PVD树突分泌神经肽来调节肌肉收缩。令人惊讶的是，突变一种名为sax-1的基因可以恢复树突的形成和细胞器的运输。我们的发现揭示了树突状细胞骨架组装和细胞内运输的新调控机制。
Cortical actin, a thin layer of actin network underneath the plasma membranes, plays critical roles in numerous processes, such as cell morphogenesis and migration. Neurons often grow highly branched dendrite morphologies, which is crucial for neural circuit assembly. It is still poorly understood how cortical actin assembly is controlled in dendrites and whether it is critical for dendrite development, maintenance and function. In the present study, we find that knock-out of C. elegans chdp-1, which encodes a cell cortex-localized protein, causes dendrite formation defects in the larval stages and spontaneous dendrite degeneration in adults. Actin assembly in the dendritic growth cones is significantly reduced in the chdp-1 mutants. PVD neurons sense muscle contraction and act as proprioceptors. Loss of chdp-1 abolishes proprioception, which can be rescued by expressing CHDP-1 in the PVD neurons. In the high-ordered branches, loss of chdp-1 also severely affects the microtubule cytoskeleton assembly, intracellular organelle transport and neuropeptide secretion. Interestingly, knock-out of sax-1, which encodes an evolutionary conserved serine/threonine protein kinase, suppresses the defects mentioned above in chdp-1 mutants. Thus, our findings suggest that CHDP-1 and SAX-1 function in an opposing manner in the multi-dendritic neurons to modulate cortical actin assembly, which is critical for dendrite development, maintenance and function. Neurons often grow highly-branched cell protrusions called “dendrites” to receive signals from the environment or other neurons. Inside these cells, two types of cytoskeletons, known as the actin cytoskeleton and microtubule cytoskeleton, play essential roles during dendritic branching, growth and function. However, it is not fully understood how the dynamics of the neuronal cytoskeletons are controlled. Using the nematode C. elegans (a tiny roundworm found in the soil) as a research model, we found that CHDP-1, a protein localized on the cell cortex, plays a vital role in the formation of actin and microtubule cytoskeleton in the dendrites. Mutations in chdp-1 cause defective dendrite branching and transport of intracellular organelles. chdp-1 mutants cannot secrete neuropeptides from the PVD dendrites to module the muscle contraction. Surprisingly, mutating a gene called sax-1, which encodes a protein kinase, restores dendrite formation and organelle transport. Our findings reveal novel regulatory mechanisms for dendritic cytoskeleton assembly and intracellular transport.
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影响因子：
3.3
作者：
Gleason AM;Nguyen KC;Hall DH;Grant BD
通讯作者：
Grant BD
影响因子：
64.5
作者：
Emoto, K;He, Y;Jan, YN
通讯作者：
Jan, YN
DOI：
10.1073/pnas.1605707113
发表时间：
2016-05-24
影响因子：
11.1
作者：
He, Jiang;Zhou, Ruobo;Zhuang, Xiaowei
通讯作者：
Zhuang, Xiaowei
影响因子：
4.6
作者：
Aguirre-Chen, Cristina;Buelow, Hannes E.;Kaprielian, Zaven
通讯作者：
Kaprielian, Zaven
影响因子：
2.7
作者：
Fang X;Adler PN
通讯作者：
Adler PN