Lrrk regulates the dynamic profile of dendritic Golgi outposts through the golgin Lava lamp

J Cell Biol. 2015 Aug 3;210(3):471-83. doi: 10.1083/jcb.201411033. Epub 2015 Jul 27.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cell Line
  • Dendrites / metabolism*
  • Drosophila Proteins / biosynthesis
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Dyneins / metabolism
  • Golgi Apparatus / metabolism*
  • Membrane Proteins / metabolism*
  • Microtubule-Associated Proteins / metabolism*
  • Protein Serine-Threonine Kinases / biosynthesis
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein Transport / genetics


  • Drosophila Proteins
  • Lva protein, Drosophila
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • LRRK protein, Drosophila
  • Protein Serine-Threonine Kinases
  • Dyneins