Iwasaki K, Toyonaga R
Laboratory of Molecular Neurobiology, National Institute of Bioscience and Human Technology, 1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.
EMBO J. 2000 Sep 1;19(17):4806-16. doi: 10.1093/emboj/19.17.4806.
Guanine nucleotide exchange is essential for Rab GTPase activities in regulating intracellular vesicle trafficking. This exchange process is facilitated by guanine nucleotide exchange factor (GEF). Previously, we identified Caenorhabditis elegans AEX-3 as a GEF for Rab3 GTPase. Here we demonstrate that AEX-3 regulates neural activities through a second, previously unrecognized pathway via interactions with the novel protein CAB-1. CAB-1 is 425 amino acids long and has an 80 amino acid motif in common with the mouse neural protein NPDC-1. cab-1 and rab-3 mutants have different behavioral defects, and RAB-3 localization and function are apparently normal in cab-1 mutants, indicating that the CAB-1 pathway is distinct from the RAB-3 pathway. The aex-3 mutant phenotype resembles the sum of the rab-3 and cab-1 mutant phenotypes, indicating that AEX-3 regulates two different pathways for neural activities. We propose that connection of multiple pathways may be an important feature of Rab GEFs to coordinate various cellular events.
鸟嘌呤核苷酸交换对于Rab GTP酶在调节细胞内囊泡运输中的活性至关重要。这种交换过程由鸟嘌呤核苷酸交换因子（GEF）促进。此前，我们将秀丽隐杆线虫的AEX-3鉴定为Rab3 GTP酶的GEF。在此我们证明，AEX-3通过与新蛋白CAB-1相互作用，经由第二条此前未被识别的途径调节神经活动。CAB-1长425个氨基酸，与小鼠神经蛋白NPDC-1有一个80个氨基酸的基序相同。cab-1和rab-3突变体有不同的行为缺陷，且在cab-1突变体中RAB-3的定位和功能明显正常，这表明CAB-1途径与RAB-3途径不同。aex-3突变体表型类似于rab-3和cab-1突变体表型的总和，表明AEX-3调节神经活动的两条不同途径。我们提出，多条途径的连接可能是Rab GEF协调各种细胞事件的一个重要特征。
