The Caenorhabditis elegans voltage-gated calcium channel subunits UNC-2 and UNC-36 and the calcium-dependent kinase UNC-43/CaMKII regulate neuromuscular junction morphology.
The Caenorhabditis elegans voltage-gated calcium channel subunits UNC-2 and UNC-36 and the calcium-dependent kinase UNC-43/CaMKII regulate neuromuscular junction morphology.
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DOI：
10.1186/1749-8104-8-10
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发表时间：
2013-05-10
影响因子：
3.6
通讯作者：
Ackley BD
中科院分区：
文献类型：
--
作者：
Caylor RC;Jin Y;Ackley BD
秀丽隐杆线虫保守蛋白NID-1/nidogen和PTP-3A/LAR-RPTP的功能是有效地将突触前支架蛋白SYD-2/α-liprin定位在活性区。这些分子的功能丧失导致神经肌肉接头的大小、形态和间距的缺陷。在这里，我们表明Cav 2样电压门控钙通道（VGCC）蛋白，CaM-2和CaM-36，以及钙调蛋白激酶II（CaMKII），CaM-43，在C.优雅的unc-2、unc-36或unc-43的功能丧失导致GABA能神经肌肉接头（NMJ）稍大，但可以抑制nid-1/nidogen或ptp-3/LAR突变体中发现的突触形态缺陷。unc-43中的一个功能获得性突变导致了与nid-1突变体中发现的缺陷相似的缺陷。egl-19、Cav 1-like、cca-1、Cav 3-like、α1亚基或第二个α2/δ亚基tag-180的突变不能抑制nid-1，表明unc-2与突触细胞外基质（ECM）成分巢蛋白之间存在特异性相互作用。在延时显微镜研究中使用突触囊泡标记物，我们观察到GABA能运动神经元在幼虫发育后期添加NMJ样结构。突触终扣附加似乎至少以两种方式形成：（1）从头形成，其中一簇囊泡似乎合并，或（2）当单个点扩大，然后分裂形成两个离散的荧光点。与野生型动物相比，我们发现unc-2突变体表现出减少的NMJ动力学，在类似的发育阶段观察到较少的分裂。我们鉴定了C12 -2/C12 -36 VGCC和C12 -43/CaMKII是C. elegans突触发生β 2在突触形成中具有适度的作用，但在调节生物体发育期间发生的突触大小和形态的动态变化中具有更广泛的作用。在第4幼虫期晚期（L4），野生型动物表现出与在缺乏NID-1/PTP-3粘附的动物中发现的突触形态相似的突触形态，以及具有NID-43的组成性激活的那些突触形态。遗传证据表明，VGCC和NID-1/PTP-3粘附复合物在突触发育中提供相反的功能，表明突触粘附的调节可能是C.优雅的
The conserved Caenorhabditis elegans proteins NID-1/nidogen and PTP-3A/LAR-RPTP function to efficiently localize the presynaptic scaffold protein SYD-2/α-liprin at active zones. Loss of function in these molecules results in defects in the size, morphology and spacing of neuromuscular junctions. Here we show that the Cav2-like voltage-gated calcium channel (VGCC) proteins, UNC-2 and UNC-36, and the calmodulin kinase II (CaMKII), UNC-43, function to regulate the size and morphology of presynaptic domains in C. elegans. Loss of function in unc-2, unc-36 or unc-43 resulted in slightly larger GABAergic neuromuscular junctions (NMJs), but could suppress the synaptic morphology defects found in nid-1/nidogen or ptp-3/LAR mutants. A gain-of-function mutation in unc-43 caused defects similar to those found in nid-1 mutants. Mutations in egl-19, Cav1-like, or cca-1, Cav3-like, α1 subunits, or the second α2/δ subunit, tag-180, did not suppress nid-1, suggesting a specific interaction between unc-2 and the synaptic extracellular matrix (ECM) component nidogen. Using a synaptic vesicle marker in time-lapse microscopy studies, we observed GABAergic motor neurons adding NMJ-like structures during late larval development. The synaptic bouton addition appeared to form in at least two ways: (1) de novo formation, where a cluster of vesicles appeared to coalesce, or (2) when a single punctum became enlarged and then divided to form two discrete fluorescent puncta. In comparison to wild type animals, we found unc-2 mutants exhibited reduced NMJ dynamics, with fewer observed divisions during a similar stage of development. We identified UNC-2/UNC-36 VGCCs and UNC-43/CaMKII as regulators of C. elegans synaptogenesis. UNC-2 has a modest role in synapse formation, but a broader role in regulating dynamic changes in the size and morphology of synapses that occur during organismal development. During the late 4th larval stage (L4), wild type animals exhibit synaptic morphologies that are similar to those found in animals lacking NID-1/PTP-3 adhesion, as well as those with constitutive activation of UNC-43. Genetic evidence indicates that the VGCCs and the NID-1/PTP-3 adhesion complex provide opposing functions in synaptic development, suggesting that modulation of synaptic adhesion may underlie synapse development in C. elegans.
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影响因子：
34.7
作者：
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