The small G protein Arl8 contributes to lysosomal function and long-range axonal transport in Drosophila.
The small G protein Arl8 contributes to lysosomal function and long-range axonal transport in Drosophila.
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DOI：
10.1242/bio.035964
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发表时间：
2018-09-05
期刊：
影响因子：
2.4
通讯作者：
Munro S
中科院分区：
文献类型：
--
作者：
Rosa-Ferreira C;Sweeney ST;Munro S
小的GTPase ar18已成为溶酶体上的主要调节GTPase。在哺乳动物细胞中的研究表明，它既调节与晚期内体的融合，也调节溶酶体的运动。在其活跃的gtp结合状态下，它向溶酶体招募HOPS（同型融合和蛋白质分选）内体系带复合体以及将溶酶体与微管马达连接起来的蛋白质，如运动蛋白接头PLEKHM2。为了进一步了解ar18生物学，我们研究了单个果蝇的同源性。果蝇ar18对生存能力至关重要，突变细胞的有丝分裂克隆能够继续分裂，但显示出晚期内吞途径的扰动。缺乏ar18的后代死于晚期幼虫，伴有运动瘫痪，特征是神经元功能缺陷。运动神经元中ar18的表达挽救了这种表型。在突变幼虫中对这些神经元的检查显示，突触和轴突变小，含有突触成分的载体水平升高。亲和层析揭示了果蝇ar18与HOPS复合物的结合，以及与果蝇同源的RILP的结合，RILP是一种蛋白质，在哺乳动物中，将动力蛋白募集到晚期内体，已知动力蛋白是神经元运输所必需的。因此果蝇ar18通过至少两种不同的效应器控制晚期内吞功能和转运。摘要：果蝇ar18对生存能力至关重要，并且是后期内吞途径和轴突远程运输的正常功能所必需的。
The small GTPase Arl8 has emerged as a major regulatory GTPase on lysosomes. Studies in mammalian cells have shown that it regulates both fusion with late endosomes and also lysosomal motility. In its active GTP-bound state, it recruits to lysosomes the HOPS (homotypic fusion and protein sorting) endosomal tethering complex and also proteins that link lysosomes to microtubule motors such as the kinesin adaptor PLEKHM2. To gain further insights into Arl8 biology, we examined the single Drosophila ortholog. Drosophila Arl8 is essential for viability, and mitotic clones of mutant cells are able to continue to divide but show perturbation of the late endocytic pathway. Progeny-lacking Arl8 die as late larvae with movement-paralysis characteristic of defects in neuronal function. This phenotype was rescued by expression of Arl8 in motor neurons. Examination of these neurons in the mutant larvae revealed smaller synapses and axons with elevated levels of carriers containing synaptic components. Affinity chromatography revealed binding of Drosophila Arl8 to the HOPS complex, and to the Drosophila ortholog of RILP, a protein that, in mammals, recruits dynein to late endosomes, with dynein being known to be required for neuronal transport. Thus Drosophila Arl8 controls late endocytic function and transport via at least two distinct effectors. . Summary: Drosophila Arl8 is essential for viability and is required for normal functioning of the late endocytic pathway and for long-range transport in axons.
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影响因子：
4.5
作者：
Füger P;Sreekumar V;Schüle R;Kern JV;Stanchev DT;Schneider CD;Karle KN;Daub KJ;Siegert VK;Flötenmeyer M;Schwarz H;Schöls L;Rasse TM
通讯作者：
Rasse TM
RAB GTPases在膜交通和细胞生理学中的作用。
影响因子：
33.6
作者：
Hutagalung AH;Novick PJ
通讯作者：
Novick PJ
影响因子：
7.5
作者：
Bonifacino JS;Neefjes J
通讯作者：
Neefjes J
影响因子：
32.4
作者：
Garg S;Sharma M;Ung C;Tuli A;Barral DC;Hava DL;Veerapen N;Besra GS;Hacohen N;Brenner MB
通讯作者：
Brenner MB
影响因子：
3.4
作者：
Kaniuk, Natalia A.;Canadien, Veronica;Brumell, John H.
通讯作者：
Brumell, John H.