A BBSome Subunit Links Ciliogenesis, Microtubule Stability, and Acetylation
A BBSome Subunit Links Ciliogenesis, Microtubule Stability, and Acetylation
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DOI：
10.1016/j.devcel.2008.11.001
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发表时间：
2008-12-09
影响因子：
11.8
通讯作者：
Nachury, Maxence V.
中科院分区：
文献类型：
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作者：
Loktev, Alexander V.;Zhang, Qihong;Nachury, Maxence V.
原发性纤毛功能障碍影响Bardet-Biedl综合征（BBS）许多器官的发育和稳态。我们最近发现，七个高度保守的BBS蛋白形成一个稳定的复合物，BBSome，在膜运输和初级纤毛内的功能。我们发现了一个BBSome亚基，命名为BBIP 10。与其他BBSome亚基类似，BBIP 10定位于初级纤毛，BBIP 10仅存在于纤毛生物体中，并且BBIP 10的耗尽在斑马鱼中产生特征性BBS表型。出乎意料的是，BBIP 10是细胞质微管聚合和乙酰化所必需的，这两种功能与任何其他BBSome亚基都不共享。引人注目的是，微管蛋白脱乙酰酶HDAC 6的抑制恢复了BBIP 10耗尽细胞中的微管乙酰化，并且BBIP 10与HDAC 6物理相互作用。因此，BBSome-bound BBIP 10可能起着偶联轴丝微管乙酰化和纤毛膜生长的作用。
Primary cilium dysfunction affects the development and homeostasis of many organs in Bardet-Biedl syndrome (BBS). We recently showed that seven highly conserved BBS proteins form a stable complex, the BBSome, that functions in membrane trafficking to and inside the primary cilium. We have now discovered a BBSome subunit that we named BBIP10. Similar to other BBSome subunits, BBIP10 localizes to the primary cilium, BBIP10 is present exclusively in ciliated organisms, and depletion of BBIP10 yields characteristic BBS phenotypes in zebrafish. Unexpectedly, BBIP10 is required for cytoplasmic microtubule polymerization and acetylation, two functions not shared with any other BBSome subunits. Strikingly, inhibition of the tubulin deacetylase HDAC6 restores microtubule acetylation in BBIP10-depleted cells, and BBIP10 physically interacts with HDAC6. BBSome-bound BBIP10 may therefore function to couple acetylation of axonemal microtubules and ciliary membrane growth.