title: AP-1 clathrin adaptor and CG8538/Aftiphilin are involved in Notch signaling during eye development in Drosophila melanogaster.
abstract: Clathrin adaptor protein complex-1 (AP-1) and its accessory proteins play a role in the sorting of integral membrane proteins at the trans-Golgi network and endosomes. Their physiological functions in complex organisms, however, are not fully understood. In this study, we found that CG8538p, an uncharacterized Drosophila protein, shares significant structural and functional characteristics with Aftiphilin, a mammalian AP-1 accessory protein. The Drosophila Aftiphilin was shown to interact directly with the ear domain of γ-adaptin of Drosophila AP-1, but not with the GAE domain of Drosophila GGA. In S2 cells, Drosophila Aftiphilin and AP-1 formed a complex and colocalized at the Golgi compartment. Moreover, tissue-specific depletion of AP-1 or Aftiphilin in the developing eyes resulted in a disordered alignment of photoreceptor neurons in larval stage and roughened eyes with aberrant ommatidia in adult flies. Furthermore, AP-1-depleted photoreceptor neurons showed an intracellular accumulation of a Notch regulator, Scabrous, and downregulation of Notch by promoting its degradation in the lysosomes. These results suggest that AP-1 and Aftiphilin are cooperatively involved in the intracellular trafficking of Notch during eye development in Drosophila.
authors.affiliation: Department of Anatomy and Histology, Fukushima Medical University, 1 Hikarigaoka, Fukushima, Fukushima 960-1295, Japan. kametaks@fmu.ac.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kametaka
authors.forename: Ai
authors.initials: A
authors.lastname: Kametaka
authors.forename: Shinichi
authors.initials: S
authors.lastname: Yonekura
authors.forename: Mineyuki
authors.initials: M
authors.lastname: Haruta
authors.forename: Seiichi
authors.initials: S
authors.lastname: Takenoshita
authors.forename: Satoshi
authors.initials: S
authors.lastname: Goto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Waguri
mesh_terms: D033982:Adaptor Protein Complex gamma Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002451:Cell Compartmentation; D002460:Cell Line; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism; D005123:Eye / Q000254:growth & development* / Q000378:metabolism*; D005124:Eye Abnormalities / Q000235:genetics / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D017956:Photoreceptor Cells, Invertebrate / Q000166:cytology / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D034622:RNA Interference; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000737:chemistry / Q000378:metabolism*; D050656:Transcription Factor AP-2 / Q000737:chemistry / Q000378:metabolism; D021601:trans-Golgi Network / Q000378:metabolism
chemical_list: C538998:AFTPH protein, human; D033982:Adaptor Protein Complex gamma Subunits; D002352:Carrier Proteins; D029721:Drosophila Proteins; D006023:Glycoproteins; C497759:N protein, Drosophila; D009419:Nerve Tissue Proteins; D051880:Receptors, Notch; C493674:TfAP-2 protein, Drosophila; D018808:Transcription Factor AP-1; D050656:Transcription Factor AP-2; C066579:sca protein, Drosophila