Bchs, a BEACH domain protein, antagonizes Rab11 in synapse morphogenesis and other developmental events

被引:74
作者
Khodosh, Rita
Augsburger, Adela
Schwarz, Thomas L.
Garrity, Paul A.
机构
[1] MIT, Dept Biol, Cambridge, MA 02139 USA
[2] Harvard Univ, Sch Med, Childrens Hosp, Div Neurosci, Boston, MA 02115 USA
[3] Brandeis Univ, Dept Biol, Waltham, MA 02454 USA
来源
DEVELOPMENT | 2006年 / 133卷 / 23期
关键词
BEACH domain; vesicle trafficking; neuromuscular junction; bouton; bristle development; Drosophila;
D O I
10.1242/dev.02650
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:4655 / 4665
页数:11
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