https://scholars.lib.ntu.edu.tw/handle/123456789/520050
標題: | Lrrk regulates the dynamic profile of dendritic Golgi outposts through the golgin Lava lamp | 作者: | CHIN-HSIEN LIN Li H. Lee Y.-N. Cheng Y.-J. RUEY-MEEI WU Chien C.-T. |
公開日期: | 2015 | 出版社: | Rockefeller University Press | 卷: | 210 | 期: | 3 | 起(迄)頁: | 471-483 | 來源出版物: | Journal of Cell Biology | 摘要: | 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. ? 2015 Lin et al. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84946592404&doi=10.1083%2fjcb.201411033&partnerID=40&md5=50724759cfc1f80090cc156070a3ccbd https://scholars.lib.ntu.edu.tw/handle/123456789/520050 |
ISSN: | 0021-9525 | DOI: | 10.1083/jcb.201411033 | SDG/關鍵字: | dynein adenosine triphosphatase; dynein heavy chain; golgin lava lamp; leucine rich repeat kinase; leucine rich repeat kinase 2; protein; protein serine threonine kinase; unclassified drug; Drosophila protein; dynein adenosine triphosphatase; Lava lamp protein, Drosophila; LRRK protein, Drosophila; membrane protein; microtubule associated protein; protein serine threonine kinase; animal cell; Article; controlled study; dendrite; Drosophila melanogaster; enzyme activity; gene overexpression; Golgi complex; golgi membrane; Golgi outpost; heavy chain; loss of function mutation; nerve cell degeneration; nerve cell differentiation; nonhuman; perikaryon; priority journal; protein function; protein protein interaction; regulatory mechanism; animal; biosynthesis; cell line; dendrite; genetics; Golgi complex; metabolism; protein transport; transgenic animal; Animals; Animals, Genetically Modified; Cell Line; Dendrites; Drosophila melanogaster; Drosophila Proteins; Dyneins; Golgi Apparatus; Membrane Proteins; Microtubule-Associated Proteins; Protein Transport; Protein-Serine-Threonine Kinases |
顯示於: | 醫學系 |
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