title: A novel protein LZTFL1 regulates ciliary trafficking of the BBSome and Smoothened.
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.
authors.affiliation: Department of Pediatrics, University of Iowa College of Medicine, Iowa City, Iowa, USA.
authors.forename: Seongjin
authors.initials: S
authors.lastname: Seo
authors.forename: Qihong
authors.initials: Q
authors.lastname: Zhang
authors.forename: Kevin
authors.initials: K
authors.lastname: Bugge
authors.forename: David K
authors.initials: DK
authors.lastname: Breslow
authors.forename: Charles C
authors.initials: CC
authors.lastname: Searby
authors.forename: Maxence V
authors.initials: MV
authors.lastname: Nachury
authors.forename: Val C
authors.initials: VC
authors.lastname: Sheffield
mesh_terms: D000818:Animals; D020788:Bardet-Biedl Syndrome / Q000235:genetics / Q000378:metabolism*; D002923:Cilia / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D000072086:Smoothened Receptor; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C506281:BBS4 protein, mouse; D053823:Hedgehog Proteins; C431701:LZTFL1 protein, human; C486612:Lztfl1 protein, mouse; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; C491023:SMO protein, human; D000072086:Smoothened Receptor; D014157:Transcription Factors
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