title: Activity-dependent facilitation of Synaptojanin and synaptic vesicle recycling by the Minibrain kinase.
abstract: Phosphorylation has emerged as a crucial regulatory mechanism in the nervous system to integrate the dynamic signalling required for proper synaptic development, function and plasticity, particularly during changes in neuronal activity. Here we present evidence that Minibrain (Mnb; also known as Dyrk1A), a serine/threonine kinase implicated in autism spectrum disorder and Down syndrome, is required presynaptically for normal synaptic growth and rapid synaptic vesicle endocytosis at the Drosophila neuromuscular junction (NMJ). We find that Mnb-dependent phosphorylation of Synaptojanin (Synj) is required, in vivo, for complex endocytic protein interactions and to enhance Synj activity. Neuronal stimulation drives Mnb mobilization to endocytic zones and triggers Mnb-dependent phosphorylation of Synj. Our data identify Mnb as a synaptic kinase that promotes efficient synaptic vesicle recycling by dynamically calibrating Synj function at the Drosophila NMJ, and in turn endocytic capacity, to adapt to conditions of high synaptic activity.
authors: 1] Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA [2] Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
authors: Chun-Kan
authors: CK
authors: Chen
authors: 1] Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA [2].
authors: Catherine
authors: C
authors: Bregere
authors: 1] Department of Neurobiology, University of Southern California, Los Angeles, California 90089, USA [2].
authors: Jeremy
authors: J
authors: Paluch
authors: Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
authors: Jason F
authors: JF
authors: Lu
authors: Department of Neurobiology, University of Southern California, Los Angeles, California 90089, USA.
authors: Dion K
authors: DK
authors: Dickman
authors: 1] Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA [2] Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
authors: Karen T
authors: KT
authors: Chang
mesh_terms: D000818:Animals; D004330:Drosophila / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000201:enzymology / Q000235:genetics; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000201:enzymology; D013572:Synaptic Vesicles / Q000201:enzymology* / Q000235:genetics; D000097603:Dyrk Kinases
chemical_list: D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D010744:Phosphoric Monoester Hydrolases; D017346:Protein Serine-Threonine Kinases; C092066:mnb protein, Drosophila; D000097603:Dyrk Kinases; C097702:synaptojanin