mec-15 Encodes an F-Box Protein Required for Touch Receptor Neuron Mechanosensation, Synapse Formation and Development
mec-15 Encodes an F-Box Protein Required for Touch Receptor Neuron Mechanosensation, Synapse Formation and Development
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DOI：
10.1534/genetics.109.105726
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发表时间：
2009-10-01
期刊：
影响因子：
3.3
通讯作者：
Chalfie, Martin
中科院分区：
文献类型：
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作者：
Bounoutas, Alexander;Zheng, Qun;Chalfie, Martin
选择性蛋白质降解是神经元发育和突触发生的关键调节因子。靶向蛋白质降解的复合物通常含有F-box蛋白质。在这里，我们表征MEC-15，一个F-盒蛋白与WD重复，这是必需的秀丽隐杆线虫触摸受体神经元（TRN）的发展和功能。mec-15的突变导致TRN触觉敏感性、化学突触形成和细胞体形态的缺陷。所有mec-15突变体表型都通过由MAPKKK DLK-1、MAPKK MKK-4和p38 MAPK PMK-3组成的MAP激酶途径中的突变而增强。编码E3泛素连接酶的rpm-1基因突变，该酶负调节该途径以促进突触发生，仅抑制mec-15细胞体缺陷。因此，MEC-15与RPM-1平行起作用，暗示TRN发育中的第二种蛋白质降解途径。此外，所有mec-15表型可被编码β-微管蛋白的mec-7中的突变显性抑制，并且被编码α-微管蛋白的mec-12中的突变显性增强。由于MEC-15表型取决于这些微管蛋白的相对水平，MEC-15可能靶向其功能受这些水平影响的蛋白质。
Selective protein degradation is a key regulator of neuronal development and synaptogenesis. Complexes that target proteins for degradation often contain F-box proteins. Here we characterize MEC-15, an F-box protein with WD repeats, which is required for the development and function of Caenorhabditis elegans touch receptor neurons (TRNs). Mutations in mec-15 produce defects in TRN touch sensitivity, chemical synapse formation, and cell-body morphology. All mec-15 mutant phenotypes are enhanced by mutations in a MAP kinase pathway composed of the MAPKKK DLK-1, the MAPKK MKK-4, and the p38 MAPK PMK-3. A Mutation of the rpm-1 gene, which encodes an E3 ubiquitin ligase that negatively regulates this pathway to promote synaptogenesis, Suppresses only the mec-15 cell-body defect. Thus, MEC-15 acts in parallel with RPM-1, implicating a second protein degradation pathway in TRN development. In addition, all mec-15 phenotypes can be dominantly suppressed by mutations in mec-7, which encodes a beta-tubulin, and dominantly enhanced by mutations in mec-12, which encodes an alpha-tubulin. Since mec-15 phenotypes depend on the relative levels of these tubulins, MEC-15 may target proteins whose function is affected by these levels.