title: Higher order signaling: ARL2 as regulator of both mitochondrial fusion and microtubule dynamics allows integration of 2 essential cell functions.
abstract: ARL2 is among the most highly conserved proteins, predicted to be present in the last eukaryotic common ancestor, and ubiquitously expressed. Genetic screens in multiple model organisms identified ARL2, and its cytosolic binding partner cofactor D (TBCD), as important in tubulin folding and microtubule dynamics. Both ARL2 and TBCD also localize to centrosomes, making it difficult to dissect these effects. A growing body of evidence also has found roles for ARL2 inside mitochondria, as a regulator of mitochondrial fusion. Other studies have revealed roles for ARL2, in concert with its closest paralog ARL3, in the traffic of farnesylated cargos between membranes and specifically to cilia and photoreceptor cells. Details of each of these signaling processes continue to emerge. We summarize those data here and speculate about the potential for cross-talk or coordination of cell regulation, termed higher order signaling, based upon the use of a common GTPase in disparate cell functions.
authors.affiliation: a Department of Biochemistry , Emory University School of Medicine , Atlanta , GA , USA.
authors.forename: Joshua W
authors.initials: JW
authors.lastname: Francis
authors.affiliation: a Department of Biochemistry , Emory University School of Medicine , Atlanta , GA , USA.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Turn
authors.affiliation: a Department of Biochemistry , Emory University School of Medicine , Atlanta , GA , USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Newman
authors.affiliation: a Department of Biochemistry , Emory University School of Medicine , Atlanta , GA , USA.
authors.forename: Cara
authors.initials: C
authors.lastname: Schiavon
authors.affiliation: a Department of Biochemistry , Emory University School of Medicine , Atlanta , GA , USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kahn
mesh_terms: D000818:Animals; D018385:Centrosome / Q000378:metabolism; D002923:Cilia / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D063154:Mitochondrial Dynamics; D010786:Photoreceptor Cells / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D008869:Microtubule-Associated Proteins; C418662:TBCD protein, human; C410130:ARL2 protein, human; D019204:GTP-Binding Proteins
keywords: ARF family GTPases; ARL2; ARL3; BART; PDE6D; TBCD; cofactor D; microtubule dynamics; mitochondrial fusion