title: MAP1B rescues LRRK2 mutant-mediated cytotoxicity.
abstract: 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.
authors.affiliation: National Neuroscience Institute, SGH Campus, Singapore, Singapore. sharon.chan@live.com.sg.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Chan
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Chua
authors.forename: Dario C
authors.initials: DC
authors.lastname: Angeles
authors.forename: Eng-King
authors.initials: EK
authors.lastname: Tan
mesh_terms: D016923:Cell Death; D002460:Cell Line; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D050505:Mutant Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport; D020798:Two-Hybrid System Techniques
chemical_list: D008869:Microtubule-Associated Proteins; D050505:Mutant Proteins; C085284:microtubule-associated protein 1B; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases
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