Rab3GEP is the non-redundant guanine nucleotide exchange factor for Rab27a in melanocytes.
Rab3GEP is the non-redundant guanine nucleotide exchange factor for Rab27a in melanocytes.
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DOI：
10.1074/jbc.m804134200
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发表时间：
2008-08-22
期刊：
影响因子：
--
通讯作者：
Seabra MC
中科院分区：
文献类型：
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作者：
Figueiredo AC;Wasmeier C;Tarafder AK;Ramalho JS;Baron RA;Seabra MC
Rab gtpase调节囊泡运输途径的离散步骤。Rabs需要特定的鸟嘌呤核苷酸交换因子（gef）激活，刺激GDP交换GTP。Rab27a控制运动和调节分泌颗粒和相关细胞器的胞吐。在黑素细胞中，Rab27a通过募集嗜黑素和肌球蛋白Va来调节成熟黑素小体的外周运输。我们将Rab3GEP（先前作为Rab3a的GEF分离）鉴定为非冗余的Rab27a GEF。与Rab27a缺失的灰白黑色素细胞类似，rab3gep缺失的细胞在核周区域显示黑色素小体聚集，并且Rab27a效应体Mlph缺失。在缺乏Rab3GEP的细胞中，Rab27a-GTP的水平降低，这与它作为激活剂的作用一致。重组Rab3GEP在体外表现出对Rab27a和Rab27b的鸟嘌呤核苷酸交换活性，以及先前报道的对Rab3的活性。我们的研究结果表明Rab GEF的作用是混杂的，并表明相关但功能不同的Rab亚家族成员可以被共同的激活因子控制。
Rab GTPases regulate discrete steps in vesicular transport pathways. Rabs require activation by specific guanine nucleotide exchange factors (GEFs) that stimulate the exchange of GDP for GTP. Rab27a controls motility and regulated exocytosis of secretory granules and related organelles. In melanocytes, Rab27a regulates peripheral transport of mature melanosomes by recruiting melanophilin and myosin Va. Here, we studied the activation of Rab27a in melanocytes. We identify Rab3GEP, previously isolated as a GEF for Rab3a, as the non-redundant Rab27a GEF. Similar to Rab27a-deficient ashen melanocytes, Rab3GEP-depleted cells show both clustering of melanosomes in the perinuclear area and loss of the Rab27a effector Mlph. Consistent with a role as an activator, levels of Rab27a-GTP are decreased in cells lacking Rab3GEP. Recombinant Rab3GEP exhibits guanine nucleotide exchange activity against Rab27a and Rab27b in vitro, in addition to its previously documented activity against Rab3. Our results indicate promiscuity in Rab GEF action and suggest that members of related but functionally distinct Rab subfamilies can be controlled by common activators.