Loktev Alexander V, Zhang Qihong, Beck John S, Searby Charles C, Scheetz Todd E, Bazan J Fernando, Slusarski Diane C, Sheffield Val C, Jackson Peter K, Nachury Maxence V
Genentech, Inc., South San Francisco, CA 94080, USA.
Dev Cell. 2008 Dec;15(6):854-65. doi: 10.1016/j.devcel.2008.11.001.
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.
原发性纤毛功能障碍影响巴德-比德尔综合征（BBS）中许多器官的发育和内环境稳定。我们最近发现，七种高度保守的BBS蛋白形成一个稳定的复合物——BBSome，其在向初级纤毛和初级纤毛内部的膜转运中发挥作用。我们现在发现了一个BBSome亚基，我们将其命名为BBIP10。与其他BBSome亚基类似，BBIP10定位于初级纤毛，仅存在于有纤毛的生物体中，并且在斑马鱼中敲除BBIP10会产生典型的BBS表型。出乎意料的是，细胞质微管聚合和乙酰化需要BBIP10，这是其他任何BBSome亚基都不具备的两种功能。引人注目的是，抑制微管蛋白脱乙酰酶HDAC6可恢复BBIP10敲除细胞中的微管乙酰化，并且BBIP10与HDAC6存在物理相互作用。因此，与BBSome结合的BBIP10可能起到连接轴丝微管乙酰化和纤毛膜生长的作用。
