title: AF6/s-afadin is a dual residency protein and localizes to a novel subnuclear compartment.
abstract: The AF6/afadin protein is a component of cell membranes at specialized sites of cell-cell contact. Two main splice variants exist, known as l- and s-afadin, respectively. L-afadin is widely expressed in cells of epithelial origin, whilst s-afadin expression is restricted to the brain. Here we demonstrate that the short form of AF6/s-afadin is a dual residency protein able to localize to the plasma membrane or nucleus whilst the long form of AF6, l-afadin is unable to localize to the nucleus. AF6/s-afadin clusters in a distinctive speckled pattern in the nucleus, but is unable to do so when cell cycle progression is inhibited at the G(1)/S or G(2)/M checkpoints. The formation of AF6/s-afadin nuclear bodies is also sensitive to the transcriptional activity of the cell with inhibition of RNA polymerase activity abolishing AF6/s-afadin nuclear clustering. AF6/s-afadin nuclear bodies localize to a novel subnuclear compartment, failing to colocalize with other known nuclear bodies. Formation of the AF6/s-afadin nuclear foci can be regulated by specific growth factor receptor mediated signaling events and by cytoplasmic tyrosine kinases, but does not correlate with tyrosine phosphorylation of AF6/s-afadin. AF6/s-afadin is a candidate for mediating control of cellular growth processes by regulated translocation to the nucleus.
authors.affiliation: Department of Surgery, University of Melbourne, Clinical Sciences Building, Royal Melbourne Hospital, Parkville, VIC, Australia. mbuchert@univ-montp1.fr
authors.forename: Michael
authors.initials: M
authors.lastname: Buchert
authors.forename: Carole
authors.initials: C
authors.lastname: Poon
authors.forename: James A J
authors.initials: JA
authors.lastname: King
authors.forename: Thomas
authors.initials: T
authors.lastname: Baechi
authors.forename: Giovanna
authors.initials: G
authors.lastname: D'Abaco
authors.forename: Frédéric
authors.initials: F
authors.lastname: Hollande
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Hovens
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D022003:Cell Nucleus Structures / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors; D004285:Dogs; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D060588:LIM Domain Proteins; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D050258:Mitosis Modulators / Q000494:pharmacology; D009218:Myosins / Q000235:genetics / Q000378:metabolism*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D009842:Oligopeptides; D010455:Peptides / Q000235:genetics; D010766:Phosphorylation; D021381:Protein Transport / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
chemical_list: C095516:AFDN protein, human; C507006:Afdn protein, rat; D060588:LIM Domain Proteins; D008840:Microfilament Proteins; D050258:Mitosis Modulators; D019384:Nucleic Acid Synthesis Inhibitors; D009842:Oligopeptides; D010455:Peptides; D011994:Recombinant Proteins; C108835:afadin; D049452:Green Fluorescent Proteins; C085706:FLAG peptide; D011505:Protein-Tyrosine Kinases; D012321:DNA-Directed RNA Polymerases; D009218:Myosins; D016547:Kinesins