title: The Interaction of CCDC104/BARTL1 with Arl3 and Implications for Ciliary Function.
abstract: Cilia are small antenna-like cellular protrusions critical for many developmental signaling pathways. The ciliary protein Arl3 has been shown to act as a specific release factor for myristoylated and farnesylated ciliary cargo molecules by binding to the effectors Unc119 and PDE6δ. Here we describe a newly identified Arl3 binding partner, CCDC104/CFAP36. Biochemical and structural analyses reveal that the protein contains a BART-like domain and is called BARTL1. It recognizes an LLxILxxL motif at the N-terminal amphipathic helix of Arl3, which is crucial for the interaction with the BART-like domain but also for the ciliary localization of Arl3 itself. These results seem to suggest a ciliary role of BARTL1, and possibly link it to the Arl3 transport network. We thus speculate on a regulatory mechanism whereby BARTL1 aids the presentation of active Arl3 to its GTPase-activating protein RP2 or hinders Arl3 membrane binding in the area of the transition zone.
authors.affiliation: Max-Planck-Institute of Molecular Physiology, Emeritus Group, Otto-Hahn-Straße 15, 44227 Dortmund, Germany.
authors.forename: Mandy
authors.initials: M
authors.lastname: Lokaj
authors.affiliation: Max-Planck-Institute of Molecular Physiology, Emeritus Group, Otto-Hahn-Straße 15, 44227 Dortmund, Germany.
authors.forename: Stefanie K
authors.initials: SK
authors.lastname: Kösling
authors.affiliation: Max-Planck-Institute of Molecular Physiology, Emeritus Group, Otto-Hahn-Straße 15, 44227 Dortmund, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Koerner
authors.affiliation: Max-Planck-Institute of Molecular Physiology, Emeritus Group, Otto-Hahn-Straße 15, 44227 Dortmund, Germany.
authors.forename: Sven M
authors.initials: SM
authors.lastname: Lange
authors.affiliation: Department of Human Genetics and Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, the Netherlands.
authors.forename: Sylvia E C
authors.initials: SE
authors.lastname: van Beersum
authors.affiliation: Department of Human Genetics and Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, the Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: van Reeuwijk
authors.affiliation: Department of Human Genetics and Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, the Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: Roepman
authors.affiliation: Medical Proteome Center, Institute for Ophthalmic Research, University of Tübingen, Nägelestrasse 5, 72074 Tübingen, Germany.
authors.forename: Nicola
authors.initials: N
authors.lastname: Horn
authors.affiliation: Medical Proteome Center, Institute for Ophthalmic Research, University of Tübingen, Nägelestrasse 5, 72074 Tübingen, Germany.
authors.forename: Marius
authors.initials: M
authors.lastname: Ueffing
authors.affiliation: Medical Proteome Center, Institute for Ophthalmic Research, University of Tübingen, Nägelestrasse 5, 72074 Tübingen, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Boldt
authors.affiliation: Max-Planck-Institute of Molecular Physiology, Emeritus Group, Otto-Hahn-Straße 15, 44227 Dortmund, Germany. Electronic address: alfred.wittinghofer@mpi-dortmund.mpg.de.
authors.forename: Alfred
authors.initials: A
authors.lastname: Wittinghofer
mesh_terms: D020727:ADP-Ribosylation Factors / Q000378:metabolism*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002923:Cilia / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D021381:Protein Transport; D011506:Proteins
chemical_list: D011506:Proteins; C557494:coiled-coil domain-containing protein 104, human; C490248:Arl3 protein, mouse; D020727:ADP-Ribosylation Factors