Chaperone complex BAG2-HSC70 regulates localization of Caenorhabditis elegans leucine-rich repeat kinase LRK-1 to the Golgi

Genes Cells. 2016 Apr;21(4):311-24. doi: 10.1111/gtc.12338. Epub 2016 Feb 8.

Abstract

Mutations in LRRK2 are linked to autosomal dominant forms of Parkinson's disease. We identified two human proteins that bind to LRRK2: BAG2 and HSC70, which are known to form a chaperone complex. We characterized the role of their Caenorhabditis elegans homologues, UNC-23 and HSP-1, in the regulation of LRK-1, the sole homologue of human LRRK2. In C. elegans, LRK-1 determines the polarized sorting of synaptic vesicle (SV) proteins to the axons by excluding SV proteins from the dendrite-specific transport machinery in the Golgi. In unc-23 mutants, SV proteins are localized to both presynaptic and dendritic endings in neurons, a phenotype also observed in lrk-1 deletion mutants. Furthermore, we isolated mutations in the hsp-1 gene that can suppress the unc-23, but not the lrk-1 defect. We show that UNC-23 determines LRK-1 localization to the Golgi apparatus in cooperation with HSP-1. These results describe a chaperone-dependent mechanism through which LRK-1 localization is regulated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / metabolism*
  • Carrier Proteins / metabolism*
  • Golgi Apparatus / metabolism*
  • HSP70 Heat-Shock Proteins / metabolism*
  • Molecular Chaperones / metabolism
  • Protein-Serine-Threonine Kinases / metabolism*
  • Synaptic Vesicles / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • HSP-1 protein, C elegans
  • HSP70 Heat-Shock Proteins
  • Molecular Chaperones
  • Unc-23 protein, C elegans
  • Unc-24 protein, C elegans
  • LRK-1 protein, C elegans
  • Protein-Serine-Threonine Kinases