title: The matrix protein Hikaru genki localizes to cholinergic synaptic clefts and regulates postsynaptic organization in the Drosophila brain.
abstract: The synaptic cleft, a crucial space involved in neurotransmission, is filled with extracellular matrix that serves as a scaffold for synaptic differentiation. However, little is known about the proteins present in the matrix and their functions in synaptogenesis, especially in the CNS. Here, we report that Hikaru genki (Hig), a secreted protein with an Ig motif and complement control protein domains, localizes specifically to the synaptic clefts of cholinergic synapses in the Drosophila CNS. The data indicate that this specific localization is achieved by capture of secreted Hig in synaptic clefts, even when it is ectopically expressed in glia. In the absence of Hig, the cytoskeletal scaffold protein DLG accumulated abnormally in cholinergic postsynapses, and the synaptic distribution of acetylcholine receptor (AchR) subunits Dα6 and Dα7 significantly decreased. hig mutant flies consistently exhibited resistance to the AchR agonist spinosad, which causes lethality by specifically activating the Dα6 subunit, suggesting that loss of Hig compromises the cholinergic synaptic activity mediated by Dα6. These results indicate that Hig is a specific component of the synaptic cleft matrix of cholinergic synapses and regulates their postsynaptic organization in the CNS.
authors.affiliation: Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Nakayama
authors.affiliation: Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555, Japan.
authors.forename: Fumiya
authors.initials: F
authors.lastname: Matsushita
authors.affiliation: Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555, Japan hama@cc.kyoto-su.ac.jp.
authors.forename: Chihiro
authors.identifier: http://orcid.org/0000-0002-4158-719X
authors.initials: C
authors.lastname: Hama
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001921:Brain / Q000502:physiology*; D001923:Brain Chemistry / Q000502:physiology; D059329:Cholinergic Neurons / Q000737:chemistry / Q000502:physiology*; D004330:Drosophila; D029721:Drosophila Proteins / Q000032:analysis / Q000502:physiology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000502:physiology*; D057907:Post-Synaptic Density / Q000737:chemistry / Q000502:physiology*; D013569:Synapses / Q000737:chemistry / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; C098696:hig protein, Drosophila
keywords: DLG; Drosophila; acetylcholine receptor; matrix; synaptic cleft; synaptogenesis