title: Arl13b regulates ciliogenesis and the dynamic localization of Shh signaling proteins.
abstract: Arl13b, a ciliary protein within the ADP-ribosylation factor family and Ras superfamily of GTPases, is required for ciliary structure but has poorly defined ciliary functions. In this paper, we further characterize the role of Arl13b in cilia by examining mutant cilia in vitro and determining the localization and dynamics of Arl13b within the cilium. Previously, we showed that mice lacking Arl13b have abnormal Sonic hedgehog (Shh) signaling; in this study, we show the dynamics of Shh signaling component localization to the cilium are disrupted in the absence of Arl13b. Significantly, we found Smoothened (Smo) is enriched in Arl13b-null cilia regardless of Shh pathway stimulation, indicating Arl13b regulates the ciliary entry of Smo. Furthermore, our analysis defines a role for Arl13b in regulating the distribution of Smo within the cilium. These results suggest that abnormal Shh signaling in Arl13b mutant embryos may result from defects in protein localization and distribution within the cilium.
authors: Department of Human Genetics, School of Medicine, Emory University, Atlanta, GA 30322, USA.
authors: Christine E
authors: CE
authors: Larkins
authors: Gladys D Gonzalez
authors: GD
authors: Aviles
authors: Michael P
authors: MP
authors: East
authors: Richard A
authors: RA
authors: Kahn
authors: Tamara
authors: T
authors: Caspary
mesh_terms: D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D002923:Cilia / Q000378:metabolism* / Q000648:ultrastructure; D004622:Embryo, Mammalian / Q000166:cytology; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000072086:Smoothened Receptor; D014404:Tubulin / Q000378:metabolism; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3
chemical_list: C560093:Arl13b protein, mouse; C000618551:Gli2 protein, mouse; C465571:Gli3 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D043562:Receptors, G-Protein-Coupled; C465570:Shh protein, mouse; C491022:Smo protein, mouse; D000072086:Smoothened Receptor; D014404:Tubulin; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3; D020727:ADP-Ribosylation Factors