@article{70a365a6aa674c14b7c6771be8822925,
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.",
author = "Chen, {Chun Kan} and Catherine Bregere and Jeremy Paluch and Lu, {Jason F.} and Dickman, {Dion K.} and Chang, {Karen T.}",
note = "Funding Information: We thank Martin Heisenberg (University of Wuzburg, Germany) for the mnb1 stock. We are grateful to Hugo Bellen (Baylor, TX, USA) for his generous sharing of UAS-PLCd1-PH-GFP flies and multiple antibodies used in this manuscript, including the Synj antibody that we renamed here to p-Synj for clarification purposes. We thank Julie Simpson (HHMI Janelia Farm, VA, USA) for gift of the nSyb-Gal4 stock and the Developmental Hybridoma Bank (Iowa, USA) for antibodies. We thank the Proteomics Core at USC for assistance with mass spectrometry data collection and analyses. We also thank Dr K.-T. Min for critical reading of the manuscript, John W. Carlson for excellent technical assistance and members of the Chang laboratory for discussion. This work was supported by grants from the National Institutes of Health (NS080946), the Jerome Lejeune Foundation, and Alzheimer{\textquoteright}s Association and Global Down Syndrome Foundation to K.T.C., and grants from the NIMH (R00 MH092351) and the Ellison Medical Foundation to D.K.D.",
year = "2014",
month = jun,
day = "30",
doi = "10.1038/ncomms5246",
language = "English",
volume = "5",
journal = "Nature communications",
issn = "2041-1723",
}