title: Lrrk regulates the dynamic profile of dendritic Golgi outposts through the golgin Lava lamp.
abstract: Constructing the dendritic arbor of neurons requires dynamic movements of Golgi outposts (GOPs), the prominent component in the dendritic secretory pathway. GOPs move toward dendritic ends (anterograde) or cell bodies (retrograde), whereas most of them remain stationary. Here, we show that Leucine-rich repeat kinase (Lrrk), the Drosophila melanogaster homologue of Parkinson's disease-associated Lrrk2, regulates GOP dynamics in dendrites. Lrrk localized at stationary GOPs in dendrites and suppressed GOP movement. In Lrrk loss-of-function mutants, anterograde movement of GOPs was enhanced, whereas Lrrk overexpression increased the pool size of stationary GOPs. Lrrk interacted with the golgin Lava lamp and inhibited the interaction between Lva and dynein heavy chain, thus disrupting the recruitment of dynein to Golgi membranes. Whereas overexpression of kinase-dead Lrrk caused dominant-negative effects on GOP dynamics, overexpression of the human LRRK2 mutant G2019S with augmented kinase activity promoted retrograde movement. Our study reveals a pathogenic pathway for LRRK2 mutations causing dendrite degeneration.
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Chin-Hsien
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan Taiwan International Graduate Program in Interdisciplinary Neuroscience, National Yang-Ming University and Academia Sinica, Taipei 115, Taiwan.
authors.forename: Hsun
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Yi-Nan
authors.initials: YN
authors.lastname: Lee
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Ying-Ju
authors.initials: YJ
authors.lastname: Cheng
authors.affiliation: Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Ruey-Meei
authors.initials: RM
authors.lastname: Wu
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan ctchien@gate.sinica.edu.tw.
authors.forename: Cheng-Ting
authors.initials: CT
authors.lastname: Chien
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002460:Cell Line; D003712:Dendrites / Q000378:metabolism*; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics; D004398:Dyneins / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; C502291:Lva protein, Drosophila; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C543697:LRRK protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D004398:Dyneins