The Bardet-Biedl syndrome protein complex is an adapter expanding the cargo range of intraflagellar transport trains for ciliary export
The Bardet-Biedl syndrome protein complex is an adapter expanding the cargo range of intraflagellar transport trains for ciliary export
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DOI：
10.1073/pnas.1713226115
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发表时间：
2018-01-30
影响因子：
11.1
通讯作者：
Lechtreck, Karl F.
中科院分区：
文献类型：
--
作者：
Liu, Peiwei;Lechtreck, Karl F.
Bardet-Biedl综合征（BBS）是由BBSome（一种保守的蛋白质复合物）缺陷引起的纤毛病变。BBSome突变影响睫状膜组成，损害基于纤毛的信号传导。BBSome调节睫状膜内容物的机制仍然未知。衣原体bbs突变体缺乏趋光性，并在睫状膜中积累磷脂酶D（PLD）。单粒子成像显示PLD通过鞭毛内转运（IFT）与BBS 4共迁移，而在BBS突变体中PLD的IFT被消除。BBSome缺乏不改变PLD进入纤毛的速率。膜缔合和PLD的N-末端58个残基对于BBSome依赖的运输和纤毛输出是充分和必要的。PLD的纤毛输出序列（CES）的替换导致PLD在具有完整BBSomes和IFT的细胞的纤毛中积累。PLD在纤毛内的积累损害趋光性，揭示PLD是趋光行为的负调节剂。我们的结论是BBSome是一个货物适配器，确保纤毛出口PLD的IFT列车调节趋光性。
Bardet-Biedl syndrome (BBS) is a ciliopathy resulting from defects in the BBSome, a conserved protein complex. BBSome mutations affect ciliary membrane composition, impairing cilia-based signaling. The mechanism by which the BBSome regulates ciliary membrane content remains unknown. Chlamydomonas bbs mutants lack phototaxis and accumulate phospholipase D (PLD) in the ciliary membrane. Single particle imaging revealed that PLD comigrates with BBS4 by intraflagellar transport (IFT) while IFT of PLD is abolished in bbs mutants. BBSome deficiency did not alter the rate of PLD entry into cilia. Membrane association and the N-terminal 58 residues of PLD are sufficient and necessary for BBSome-dependent transport and ciliary export. The replacement of PLD's ciliary export sequence (CES) caused PLD to accumulate in cilia of cells with intact BBSomes and IFT. The buildup of PLD inside cilia impaired phototaxis, revealing that PLD is a negative regulator of phototactic behavior. We conclude that the BBSome is a cargo adapter ensuring ciliary export of PLD on IFT trains to regulate phototaxis.