title: SUMOylation regulates ciliary localization of olfactory signaling proteins.
abstract: Cilia are evolutionarily conserved organelles found on many mammalian cell types, including neuronal populations. Although neuronal cilia, including those on olfactory sensory neurons (OSNs), are often delineated by localization of adenylyl cyclase 3 (AC3, also known as ADCY3), the mechanisms responsible for targeting integral membrane proteins are largely unknown. Post-translational modification by small ubiquitin-like modifier (SUMO) proteins plays an important role in protein localization processes such as nuclear-cytosolic transport. Here, we identified through bioinformatic analysis that adenylyl cyclases harbor conserved SUMOylation motifs, and show that AC3 is a substrate for SUMO modification. Functionally, overexpression of the SUMO protease SENP2 prevented ciliary localization of AC3, without affecting ciliation or cilia maintenance. Furthermore, AC3-SUMO mutants did not localize to cilia. To test whether SUMOylation is sufficient for cilia entry, we compared localization of ANO2, which possesses a SUMO motif, and ANO1, which lacks SUMOylation sites and does not localize to cilia. Introduction of SUMOylation sites into ANO1 was not sufficient for ciliary entry. These data suggest that SUMOylation is necessary but not sufficient for ciliary trafficking of select constituents, further establishing the link between ciliary and nuclear import.
authors.affiliation: Department of Pharmacology and Therapeutics, University of Florida, PO Box 100267, Gainesville, FL 32610, USA.
authors.forename: Jeremy C
authors.initials: JC
authors.lastname: McIntyre
authors.affiliation: Department of Pharmacology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Ariell M
authors.initials: AM
authors.lastname: Joiner
authors.affiliation: Department of Pharmacology and Therapeutics, University of Florida, PO Box 100267, Gainesville, FL 32610, USA.
authors.forename: Lian
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Jorge
authors.initials: J
authors.lastname: Iñiguez-Lluhí
authors.affiliation: Department of Pharmacology and Therapeutics, University of Florida, PO Box 100267, Gainesville, FL 32610, USA martensj@ufl.edu.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Martens
mesh_terms: D000262:Adenylyl Cyclases / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002923:Cilia / Q000378:metabolism*; D004285:Dogs; D057809:HEK293 Cells; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D008969:Molecular Sequence Data; D021381:Protein Transport; D018035:Receptors, Odorant / Q000378:metabolism*; D015398:Signal Transduction; D058207:Sumoylation
chemical_list: D018035:Receptors, Odorant; D000262:Adenylyl Cyclases; C421784:adenylate cyclase 3
keywords: Cilia; Protein Trafficking; SUMO