2022年5月15日
Impaired cooperation between IFT74/BBS22–IFT81 and IFT25–IFT27/BBS19 causes Bardet-Biedl syndrome
Human Molecular Genetics
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- 巻
- 31
- 号
- 10
- 開始ページ
- 1681
- 終了ページ
- 1693
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1093/hmg/ddab354
- 出版者・発行元
- Oxford University Press ({OUP})
The IFT-B complex mediates ciliary anterograde protein trafficking and membrane protein export together with the BBSome. Bardet-Biedl syndrome (BBS) is caused by mutations in not only all BBSome subunits but also in some IFT-B subunits, including IFT74/BBS22 and IFT27/BBS19, which form heterodimers with IFT81 and IFT25, respectively. We found that the IFT25-IFT27 dimer binds the C-terminal region of the IFT74-IFT81 dimer and that the IFT25-IFT27-binding region encompasses the region deleted in the BBS variants of IFT74. In addition, we found that the missense BBS variants of IFT27 are impaired in IFT74-IFT81 binding and are unable to rescue the BBS-like phenotypes of IFT27-knockout (KO) cells. Furthermore, the BBS variants of IFT74 rescued the ciliogenesis defect of IFT74-KO cells, but the rescued cells demonstrated BBS-like abnormal phenotypes. Taken together, we conclude that the impaired interaction between IFT74-IFT81 and IFT25-IFT27 causes the BBS-associated ciliary defects.
- ID情報
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- DOI : 10.1093/hmg/ddab354
- ORCIDのPut Code : 104528012
- PubMed ID : 34888642