MAP1B rescues LRRK2 mutant-mediated cytotoxicity

Mol Brain. 2014 Apr 22:7:29. doi: 10.1186/1756-6606-7-29.


Leucine-rich repeat kinase 2 (LRRK2) mutations are the most common cause of dominant and sporadic Parkinson's disease (PD), a common neurodegenerative disorder. Yeast-two-hybrid screening using human LRRK2 kinase domain as bait identified microtubule associated protein 1B (MAP1B) as a LRRK2 interactor. The interacting domains were LRRK2 kinase and the light chain portion of MAP1B (LC1). LRRK2 + LC1 interaction resulted in LRRK2 kinase inhibition. LRRK2 mutants (R1441C, G2019S and I2020T) exhibited decreased endogenous LC1 expression and its co-expression with LC1 rescued LRRK2 mutant-mediated toxicity. This study presented the first data on the effects of LRRK2 + LC1 interaction and also suggested that LCI possibly rescued LRRK2 mutant-induced cytotoxicity by inhibiting LRRK2 kinase activity. Compounds that upregulate LC1 expression may therefore hold therapeutic potential for LRRK2-linked diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Death
  • Cell Line
  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Microtubule-Associated Proteins / metabolism*
  • Mutant Proteins / metabolism*
  • Phosphorylation
  • Protein Binding
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein Transport
  • Two-Hybrid System Techniques


  • Microtubule-Associated Proteins
  • Mutant Proteins
  • microtubule-associated protein 1B
  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Protein Serine-Threonine Kinases