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Differential Roles of Tubby Family Proteins in Ciliary Formation and Trafficking

 Julie J Hong  ;  Kyung Eun Kim  ;  So Young Park  ;  Jinwoong Bok  ;  Jeong Taeg Seo  ;  Seok Jun Moon 
 MOLECULES AND CELLS, Vol.44(8) : 591-601, 2021-08 
Journal Title
Issue Date
RPE1 ; TULP ; cilia ; cilia formation ; ciliary trafficking
Cilia are highly specialized organelles that extend from the cell membrane and function as cellular signaling hubs. Thus, cilia formation and the trafficking of signaling molecules into cilia are essential cellular processes. TULP3 and Tubby (TUB) are members of the tubby-like protein (TULP) family that regulate the ciliary trafficking of G-protein coupled receptors, but the functions of the remaining TULPs (i.e., TULP1 and TULP2) remain unclear. Herein, we explore whether these four structurally similar TULPs share a molecular function in ciliary protein trafficking. We found that TULP3 and TUB, but not TULP1 or TULP2, can rescue the defective cilia formation observed in TULP3-knockout (KO) hTERT RPE-1 cells. TULP3 and TUB also fully rescue the defective ciliary localization of ARL13B, INPP5E, and GPR161 in TULP3 KO RPE-1 cells, while TULP1 and TULP2 only mediate partial rescues. Furthermore, loss of TULP3 results in abnormal IFT140 localization, which can be fully rescued by TUB and partially rescued by TULP1 and TULP2. TUB's capacity for binding IFT-A is essential for its role in cilia formation and ciliary protein trafficking in RPE-1 cells, whereas its capacity for PIP2 binding is required for proper cilia length and IFT140 localization. Finally, chimeric TULP1 containing the IFT-A binding domain of TULP3 fully rescues ciliary protein trafficking, but not cilia formation. Together, these two TULP domains play distinct roles in ciliary protein trafficking but are insufficient for cilia formation in RPE-1 cells. In addition, TULP1 and TULP2 play other unknown molecular roles that should be addressed in the future.
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Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Moon, Seok Jun(문석준) ORCID logo https://orcid.org/0000-0001-7282-2888
Bok, Jin Woong(복진웅) ORCID logo https://orcid.org/0000-0003-1958-1872
Seo, Jeong Taeg(서정택) ORCID logo https://orcid.org/0000-0003-2697-0251
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