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一种新型蛋白 LZTFL1 调控 BBSome 和 Smoothened 的纤毛运输。

A novel protein LZTFL1 regulates ciliary trafficking of the BBSome and Smoothened.

机构信息

Department of Pediatrics, University of Iowa College of Medicine, Iowa City, Iowa, USA.

出版信息

PLoS Genet. 2011 Nov;7(11):e1002358. doi: 10.1371/journal.pgen.1002358. Epub 2011 Nov 3.

DOI:10.1371/journal.pgen.1002358
PMID:22072986
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3207910/
Abstract

Many signaling proteins including G protein-coupled receptors localize to primary cilia, regulating cellular processes including differentiation, proliferation, organogenesis, and tumorigenesis. Bardet-Biedl Syndrome (BBS) proteins are involved in maintaining ciliary function by mediating protein trafficking to the cilia. However, the mechanisms governing ciliary trafficking by BBS proteins are not well understood. Here, we show that a novel protein, Leucine-zipper transcription factor-like 1 (LZTFL1), interacts with a BBS protein complex known as the BBSome and regulates ciliary trafficking of this complex. We also show that all BBSome subunits and BBS3 (also known as ARL6) are required for BBSome ciliary entry and that reduction of LZTFL1 restores BBSome trafficking to cilia in BBS3 and BBS5 depleted cells. Finally, we found that BBS proteins and LZTFL1 regulate ciliary trafficking of hedgehog signal transducer, Smoothened. Our findings suggest that LZTFL1 is an important regulator of BBSome ciliary trafficking and hedgehog signaling.

摘要

许多信号蛋白，包括 G 蛋白偶联受体，定位于初级纤毛，调节细胞过程，包括分化、增殖、器官发生和肿瘤发生。Bardet-Biedl 综合征（BBS）蛋白通过介导蛋白向纤毛的运输来参与维持纤毛功能。然而，BBS 蛋白控制纤毛运输的机制尚不清楚。在这里，我们表明一种新的蛋白，亮氨酸拉链转录因子样 1（LZTFL1），与称为 BBSome 的 BBS 蛋白复合物相互作用，并调节该复合物的纤毛运输。我们还表明，所有 BBSome 亚基和 BBS3（也称为 ARL6）都需要 BBSome 进入纤毛，并且减少 LZTFL1 可恢复 BBS3 和 BBS5 耗尽细胞中 BBSome 的纤毛运输。最后，我们发现 BBS 蛋白和 LZTFL1 调节 hedgehog 信号转导蛋白 Smoothened 的纤毛运输。我们的研究结果表明，LZTFL1 是 BBSome 纤毛运输和 hedgehog 信号的重要调节剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f20d/3207910/348975fd7829/pgen.1002358.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f20d/3207910/04b0cadf2611/pgen.1002358.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f20d/3207910/61464707b854/pgen.1002358.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f20d/3207910/88fa13957622/pgen.1002358.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f20d/3207910/348975fd7829/pgen.1002358.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f20d/3207910/04b0cadf2611/pgen.1002358.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f20d/3207910/61464707b854/pgen.1002358.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f20d/3207910/88fa13957622/pgen.1002358.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f20d/3207910/348975fd7829/pgen.1002358.g004.jpg

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