ITSN-1 controls vesicle recycling at the neuromuscular junction and functions in parallel with DAB-1.
ITSN-1 controls vesicle recycling at the neuromuscular junction and functions in parallel with DAB-1.
复制标题
ITSN-1 控制神经肌肉接头处的囊泡回收，并与 DAB-1 并行发挥作用。
DOI：
10.1111/j.1600-0854.2008.00712.x
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Egan,SeanE
中科院分区：
文献类型：
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作者：
Wang,Wei;Bouhours,Magali;Gracheva,ElenaO;Liao,EdwardH;Xu,Keli;Sengar,AmeetS;Xin,Xiaofeng;Roder,John;Boone,Charles;Richmond,JanetE;Zhen,Mei;Egan,SeanE
Intersectins (Itsn) 是包含接头蛋白的保守 EH 和 SH3 结构域。在果蝇中，ITSN 需要调节突触形态，以促进有效的突触小泡回收和活力。在这里，我们报告了对秀丽隐杆线虫交叉蛋白的遗传分析。与果蝇相反，C.线虫 itn-1 蛋白无效突变体是可行的，并且表现出非常正常的运动和发育。然而，这些突变体中的运动神经元表现出大的不规则囊泡的显着增加，并在距突触前密度约 300 nm 的假定内吞热点处积累膜相关囊泡。这种缺陷恰好发生在野生型动物中内源性 ITSN-1 蛋白定位的地方，并且与突触小泡数量的显着减少和神经肌肉接头 (NMJ) 内源性突触事件频率的降低有关。 ITSN-1 与 EHS-1 (Eps15) 形成稳定的复合物，并在 hs-1 突变体中表达水平降低。因此，ITSN-1 与 EHS-1 一起协调 C 处的囊泡回收。线虫NMJ。我们还发现，itsn-1 和ehs-1 突变体在Disabled(dab-1)无效突变体背景下表现出较差的生存能力和生长。这些结果首次表明 intersectin 和 Eps15 蛋白在相同的遗传途径中发挥作用，并且似乎与网格蛋白外壳相关分选蛋白（Disabled）协同发挥作用，以提高活力。
Intersectins (Itsn) are conserved EH and SH3 domain containing adaptor proteins. InDrosophila melanogaster,ITSN is required to regulate synaptic morphology, to facilitate efficient synaptic vesicle recycling and for viability. Here, we report our genetic analysis ofCaenorhabditis elegansintersectin. In contrast toDrosophila,C. elegans itsn‐1protein null mutants are viable and display grossly normal locomotion and development. However, motor neurons in these mutants show a dramatic increase in large irregular vesicles and accumulate membrane‐associated vesicles at putative endocytic hotspots, approximately 300 nm from the presynaptic density. This defect occurs precisely where endogenous ITSN‐1 protein localizes in wild‐type animals and is associated with a significant reduction in synaptic vesicle number and reduced frequency of endogenous synaptic events at neuromuscular junctions (NMJs). ITSN‐1 forms a stable complex with EHS‐1 (Eps15) and is expressed at reduced levels inehs‐1mutants. Thus, ITSN‐1 together with EHS‐1, coordinate vesicle recycling atC. elegansNMJs. We also found that bothitsn‐1andehs‐1mutants show poor viability and growth in aDisabled(dab‐1)null mutant background. These results show for the first time that intersectin and Eps15 proteins function in the same genetic pathway, and appear to function synergistically with the clathrin‐coat‐associated sorting protein, Disabled, for viability.