Bardet-Biedl syndrome genes are important in retrograde intracellular trafficking and Kupffer's vesicle cilia function
Bardet-Biedl syndrome genes are important in retrograde intracellular trafficking and Kupffer's vesicle cilia function
复制标题
DOI：
10.1093/hmg/ddi468
复制
发表时间：
2006-03-01
影响因子：
3.5
通讯作者：
Slusarski, DC
中科院分区：
文献类型：
--
作者：
Yen, HJ;Tayeh, MK;Slusarski, DC
Bardet-Biedl 综合征 (BBS) 的特点是肥胖、视网膜病变、多指、认知障碍、肾脏和心脏异常以及高血压和糖尿病。九个已知的 BBS 基因似乎不属于同一功能类别；然而这些基因的突变会导致几乎相同的多效性表型。尽管 BBS 蛋白的精确功能尚未确定，但目前的数据支持其在纤毛功能和鞭毛内运输中的作用。为了深入了解 BBS 基因控制的生物过程，我们开始对来自斑马鱼的 6 个 BBS 直系同源物进行研究。斑马鱼 bbs2、bbs4、bbs5、bbs6、bbs7 或 bbs8 的敲低会导致库普弗囊泡 (KV) 的破坏，库普弗囊泡是一种纤毛器官，被认为在左右模式中发挥作用。 KV 缺陷是由于囊泡内纤毛的逐渐丧失造成的，并导致随后器官侧向性的改变。我们还注意到改变逆行黑素体运输的特定缺陷。这些研究首次平行比较了不同的 BBS 基因组，并证明了它们在细胞内运输中的共同作用，表明 BBS 蛋白参与一般细胞器运输。
Bardet-Biedl syndrome (BBS) is characterized by obesity, retinopathy, polydactyly, cognitive impairment, renal and cardiac anomalies as well as hypertension and diabetes. The nine known BBS genes do not appear to belong to the same functional category; yet mutation of these genes results in a nearly identical pleiotropic phenotype. Although the precise functions of the BBS proteins have yet to be determined, current data support a role in cilia function and intraflagellar transport. To gain insight into the biological processes controlled by BBS genes, we embarked on studies of six BBS orthologues from zebrafish. Knockdown of zebrafish bbs2, bbs4, bbs5, bbs6, bbs7 or bbs8 results in disruption of Kupffer's vesicle (KV), a ciliated organ thought to play a role in left-right patterning. KV defects are due to a progressive loss of cilia within the vesicle and result in subsequent alterations to organ laterality. We also note a specific defect altering retrograde melanosome transport. These studies are the first to comprehensively compare the diverse group of BBS genes in parallel and demonstrate a common role in intracellular trafficking, indicating that BBS proteins are involved in general organelle trafficking.