title: Drosophila adducin regulates Dlg phosphorylation and targeting of Dlg to the synapse and epithelial membrane.
abstract: Adducin is a cytoskeletal protein having regulatory roles that involve actin filaments, functions that are inhibited by phosphorylation of adducin by protein kinase C. Adducin is hyperphosphorylated in nervous system tissue in patients with the neurodegenerative disease amyotrophic lateral sclerosis, and mice lacking β-adducin have impaired synaptic plasticity and learning. We have found that Drosophila adducin, encoded by hu-li tai shao (hts), is localized to the post-synaptic larval neuromuscular junction (NMJ) in a complex with the scaffolding protein Discs large (Dlg), a regulator of synaptic plasticity during growth of the NMJ. hts mutant NMJs are underdeveloped, whereas over-expression of Hts promotes Dlg phosphorylation, delocalizes Dlg away from the NMJ, and causes NMJ overgrowth. Dlg is a component of septate junctions at the lateral membrane of epithelial cells, and we show that Hts regulates Dlg localization in the amnioserosa, an embryonic epithelium, and that embryos doubly mutant for hts and dlg exhibit defects in epithelial morphogenesis. The phosphorylation of Dlg by the kinases PAR-1 and CaMKII has been shown to disrupt Dlg targeting to the NMJ and we present evidence that Hts regulates Dlg targeting to the NMJ in muscle and the lateral membrane of epithelial cells by controlling the protein levels of PAR-1 and CaMKII, and consequently the extent of Dlg phosphorylation.
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia, Canada V5A 1S6.
authors.forename: Simon
authors.initials: S
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.forename: Amy
authors.initials: A
authors.lastname: Tsai
authors.forename: Tomas
authors.initials: T
authors.lastname: Kuca
authors.forename: Justina
authors.initials: J
authors.lastname: Sanny
authors.forename: Jeehwa
authors.initials: J
authors.lastname: Lee
authors.forename: Kevin
authors.initials: K
authors.lastname: Dong
authors.forename: Nicholas
authors.initials: N
authors.lastname: Harden
authors.forename: Charles
authors.initials: C
authors.lastname: Krieger
mesh_terms: D000818:Animals; D002148:Calmodulin-Binding Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D004848:Epithelium / Q000196:embryology / Q000378:metabolism*; D007814:Larva / Q000166:cytology / Q000378:metabolism; D008954:Models, Biological; D009132:Muscles / Q000378:metabolism; D016254:Mutagenesis, Insertional / Q000235:genetics; D009469:Neuromuscular Junction / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D021381:Protein Transport; D013569:Synapses / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D000099291:Adducins
chemical_list: D002148:Calmodulin-Binding Proteins; D029721:Drosophila Proteins; D025521:Tumor Suppressor Proteins; D000099291:Adducins; C108208:hts protein, Drosophila; C070350:dlg1 protein, Drosophila