title: IFT27 links the BBSome to IFT for maintenance of the ciliary signaling compartment.
abstract: Vertebrate hedgehog signaling is coordinated by the differential localization of the receptors patched-1 and Smoothened in the primary cilium. Cilia assembly is mediated by intraflagellar transport (IFT), and cilia defects disrupt hedgehog signaling, causing many structural birth defects. We generated Ift25 and Ift27 knockout mice and show that they have structural birth defects indicative of hedgehog signaling dysfunction. Surprisingly, ciliary assembly is not affected, but abnormal hedgehog signaling is observed in conjunction with ciliary accumulation of patched-1 and Smoothened. Similarly, Smoothened accumulates in cilia on cells mutated for BBSome components or the BBS binding protein/regulator Lztfl1. Interestingly, the BBSome and Lztfl1 accumulate to high levels in Ift27 mutant cilia. Because Lztfl1 mutant cells accumulate BBSome but not IFT27, it is likely that Lztfl1 functions downstream of IFT27 to couple the BBSome to the IFT particle for coordinated removal of patched-1 and Smoothened from cilia during hedgehog signaling.
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Biotech II, Suite 213, 373 Plantation Street, Worcester, MA 01605, USA.
authors.forename: Thibaut
authors.initials: T
authors.lastname: Eguether
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Biotech II, Suite 213, 373 Plantation Street, Worcester, MA 01605, USA.
authors.forename: Jovenal T
authors.initials: JT
authors.lastname: San Agustin
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Biotech II, Suite 213, 373 Plantation Street, Worcester, MA 01605, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Keady
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Jonassen
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Biotech II, Suite 213, 373 Plantation Street, Worcester, MA 01605, USA; School of Life Sciences, Tsinghua University, Renhuan Lou 413, #1 Qinghuayuan, Haidian District, Beijing 100084, China.
authors.forename: Yinwen
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Developmental Biology, University of Pittsburgh, 8111 Rangos Research Center, 530 45th Street, Pittsburgh, PA 15201, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Francis
authors.affiliation: Department of Developmental Biology, University of Pittsburgh, 8111 Rangos Research Center, 530 45th Street, Pittsburgh, PA 15201, USA.
authors.forename: Kimimasa
authors.initials: K
authors.lastname: Tobita
authors.affiliation: Section of Ophthalmology and Neurosciences, Wellcome Trust Brenner Building, Leeds Institute of Molecular Medicine, University of Leeds, St. James's University Hospital, Beckett Street, Leeds LS9 7TF, UK.
authors.forename: Colin A
authors.initials: CA
authors.lastname: Johnson
authors.affiliation: Section of Ophthalmology and Neurosciences, Wellcome Trust Brenner Building, Leeds Institute of Molecular Medicine, University of Leeds, St. James's University Hospital, Beckett Street, Leeds LS9 7TF, UK.
authors.forename: Zakia A
authors.initials: ZA
authors.lastname: Abdelhamed
authors.affiliation: Department of Developmental Biology, University of Pittsburgh, 8111 Rangos Research Center, 530 45th Street, Pittsburgh, PA 15201, USA.
authors.forename: Cecilia W
authors.initials: CW
authors.lastname: Lo
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Biotech II, Suite 213, 373 Plantation Street, Worcester, MA 01605, USA. Electronic address: gregory.pazour@umassmed.edu.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Pazour
mesh_terms: D000818:Animals; D001692:Biological Transport; D002923:Cilia / Q000378:metabolism*; D005407:Flagella / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D053823:Hedgehog Proteins; C486612:Lztfl1 protein, mouse; D011956:Receptors, Cell Surface; D014157:Transcription Factors; C000595889:intraflagellar transport 27 protein, mouse; D020691:rab GTP-Binding Proteins