Impaired cooperation between IFT74/BBS22-IFT81 and IFT25-IFT27/BBS19 causes Bardet-Biedl syndrome
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...
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Veröffentlicht in: | Human molecular genetics 2022-05, Vol.31 (10), p.1681-1693 |
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Sprache: | eng |
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Zusammenfassung: | 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. |
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ISSN: | 0964-6906 1460-2083 |
DOI: | 10.1093/hmg/ddab354 |