Bchs, a BEACH domain protein, antagonizes Rab11 in synapse morphogenesis and other developmental events
Bchs, a BEACH domain protein, antagonizes Rab11 in synapse morphogenesis and other developmental events
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DOI：
10.1242/dev.02650
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发表时间：
2006-12-01
期刊：
影响因子：
4.6
通讯作者：
Garrity, Paul A.
中科院分区：
文献类型：
--
作者：
Khodosh, Rita;Augsburger, Adela;Garrity, Paul A.
海滩蛋白是一个进化上保守的家族，其特征是存在一个海滩(Beige和Chediak-Higashi)结构域，它与膜转运有关，但它们如何与膜转运机制相互作用尚不清楚。在这里，我们展示了果蝇海滩蛋白BCHS(蓝色奶酪)在发育过程中作为Rab11的拮抗剂，Rab11是一种参与囊泡运输的小GTP酶。我们发现，BCHS功能的降低或丧失可以恢复Rab11功能降低的动物的生存能力和正常的刷毛发育，而Rab11功能的降低会加剧BCHS在眼睛中过度表达造成的缺陷。与BCHS在调节Rab11依赖的运输中的作用一致，BCHS蛋白与小泡相关，并与Rab11广泛共存于神经肌肉接头(NMJ)。在NMJ，我们发现Rab11对于突触形态发生是重要的，因为Rab11功能的降低导致Bouton密度和分支的增加。这些缺陷也被BCH的丢失所抑制。综上所述，这些数据确定BCHS是Rab11在发育过程中的拮抗剂，并揭示了这些囊泡运输的调节者在突触形态发生中的作用。这提出了一种有趣的可能性，即BCHS和其他海滩蛋白可能通过与Rab GTP酶相互作用来调节囊泡运输。
BEACH proteins, an evolutionarily conserved family characterized by the presence of a BEACH ( Beige and Chediak-Higashi) domain, have been implicated in membrane trafficking, but how they interact with the membrane trafficking machinery is unknown. Here we show that the Drosophila BEACH protein Bchs ( Blue cheese) acts during development as an antagonist of Rab11, a small GTPase involved in vesicle trafficking. We find that reduction in, or loss of, bchs function restores viability and normal bristle development in animals with reduced rab11 function, while reductions in rab11 function exacerbate defects caused by bchs overexpression in the eye. Consistent with a role for Bchs in modulating Rab11-dependent trafficking, Bchs protein is associated with vesicles and extensively colocalized with Rab11 at the neuromuscular junction (NMJ). At the NMJ, we find that rab11 is important for synaptic morphogenesis, as reductions in rab11 function cause increases in bouton density and branching. These defects are also suppressed by loss of bchs. Taken together, these data identify Bchs as an antagonist of Rab11 during development and uncover a role for these regulators of vesicle trafficking in synaptic morphogenesis. This raises the interesting possibility that Bchs and other BEACH proteins may regulate vesicle traffic via interactions with Rab GTPases.