UNC-108/RAB-2 and its effector RIC-19 are involved in dense core vesicle maturation in Caenorhabditis elegans.
UNC-108/RAB-2 and its effector RIC-19 are involved in dense core vesicle maturation in Caenorhabditis elegans.
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DOI：
10.1083/jcb.200902096
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发表时间：
2009-09-21
期刊：
影响因子：
--
通讯作者：
Eimer S
中科院分区：
文献类型：
--
作者：
Sumakovic M;Hegermann J;Luo L;Husson SJ;Schwarze K;Olendrowitz C;Schoofs L;Richmond J;Eimer S
Rab 2突变体中的不协调运动是由致密核心囊泡上的货物保留受损引起的，而不是由有缺陷的突触囊泡释放引起的。(Also请参阅爱德华兹等人在本期中的配套文章。）Rab家族的小鸟苷三磷酸酶调节细胞内囊泡运输。Rab 2在神经系统中高度表达，但其在神经元中的功能尚不清楚。在秀丽隐杆线虫中，unc-108/rab-2突变体已经基于它们的运动缺陷而被分离。我们发现rab-2突变体的运动缺陷不是由突触囊泡释放缺陷引起的，而是由致密核心囊泡（DCV）信号传导缺陷引起的。rab-2突变体中的DCV通常增大且大小不均匀;然而，它们的数量和分布不受影响。这暗示Rab 2在高尔基复合体的DCV的生物发生。我们证明，Rab 2是必要的，以防止DCV货物不适当地进入后期内体室在DCV成熟。最后，我们表明，RIC-19，C。人糖尿病自身抗原ICA 69的elegans直向同源物，也参与DCV成熟，并被激活的RAB-2募集到高尔基体膜。因此，我们提出RAB-2及其效应器RIC-19是神经元DCV成熟所必需的。
Uncoordinated movement in Rab2 mutants is caused by impaired retention of cargo on dense core vesicles, not by defective synaptic vesicle release. (Also see the companion article by Edwards et al. in this issue.) Small guanosine triphosphatases of the Rab family regulate intracellular vesicular trafficking. Rab2 is highly expressed in the nervous system, yet its function in neurons is unknown. In Caenorhabditis elegans, unc-108/rab-2 mutants have been isolated based on their locomotory defects. We show that the locomotion defects of rab-2 mutants are not caused by defects in synaptic vesicle release but by defects in dense core vesicle (DCV) signaling. DCVs in rab-2 mutants are often enlarged and heterogeneous in size; however, their number and distribution are not affected. This implicates Rab2 in the biogenesis of DCVs at the Golgi complex. We demonstrate that Rab2 is required to prevent DCV cargo from inappropriately entering late endosomal compartments during DCV maturation. Finally, we show that RIC-19, the C. elegans orthologue of the human diabetes autoantigen ICA69, is also involved in DCV maturation and is recruited to Golgi membranes by activated RAB-2. Thus, we propose that RAB-2 and its effector RIC-19 are required for neuronal DCV maturation.
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影响因子：
2.5
作者：
Gracheva EO;Hadwiger G;Nonet ML;Richmond JE
通讯作者：
Richmond JE
影响因子：
64.8
作者：
MOORE, HP;GUMBINER, B;KELLY, RB
通讯作者：
KELLY, RB
影响因子：
3.3
作者：
Chun, Denise K.;McEwen, Jason M.;Kaplan, Joshua M.
通讯作者：
Kaplan, Joshua M.
DOI：
10.1042/bss0720223
发表时间：
2005-01-01
期刊：
LIPIDS, RAFTS AND TRAFFIC
影响因子：
--
作者：
Gallop, JL;McMahon, HT
通讯作者：
McMahon, HT
影响因子：
11.4
作者：
Eimer, Stefan;Gottschalk, Alexander;Bessereau, Jean-Louis
通讯作者：
Bessereau, Jean-Louis