Journal
HUMAN MOLECULAR GENETICS
Volume 31, Issue 10, Pages 1681-1693Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddab354
Keywords
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Funding
- Japan Society for the Promotion of Science [JPJSJRP 20181701, 19H00980, 20H04904, 18H02403, 21H02427]
- Otsuka-Toshimi Scholarship Foundation
- Grants-in-Aid for Scientific Research [21H02427, 20H04904, 19H00980, 18H02403] Funding Source: KAKEN
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The impaired interaction between IFT74-IFT81 and IFT25-IFT27 is found to cause BBS-associated ciliary defects in this study.
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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