title: Chaperone complex BAG2-HSC70 regulates localization of Caenorhabditis elegans leucine-rich repeat kinase LRK-1 to the Golgi.
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.
authors: Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya, 464-8602, Japan.
authors: Takashi
authors: T
authors: Fukuzono
authors: Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya, 464-8602, Japan.
authors: Strahil Iv
authors: SI
authors: Pastuhov
authors: Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya, 464-8602, Japan.
authors: Okinobu
authors: O
authors: Fukushima
authors: Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya, 464-8602, Japan.
authors: Chun
authors: C
authors: Li
authors: Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya, 464-8602, Japan.
authors: Ayuna
authors: A
authors: Hattori
authors: National Institutes of Advanced Industrial Science and Technology, Molecular Profiling Research Center for Drug Discovery (Molprof), Kohtoh-ku, Tokyo, 135-0064, Japan.
authors: Shun-ichiro
authors: S
authors: Iemura
authors: National Institutes of Advanced Industrial Science and Technology, Molecular Profiling Research Center for Drug Discovery (Molprof), Kohtoh-ku, Tokyo, 135-0064, Japan.
authors: Tohru
authors: T
authors: Natsume
authors: Department of Molecular Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo, 101-0062, Japan.
authors: Hiroshi
authors: H
authors: Shibuya
authors: Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya, 464-8602, Japan.
authors: Hiroshi
authors: H
authors: Hanafusa
authors: Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya, 464-8602, Japan.
authors: Kunihiro
authors: K
authors: Matsumoto
authors: Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya, 464-8602, Japan.
authors: Naoki
authors: N
authors: Hisamoto
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; C000612828:HSP-1 protein, C elegans; D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; C000612827:Unc-23 protein, C elegans; C099877:Unc-24 protein, C elegans; C520110:LRK-1 protein, C elegans; D017346:Protein Serine-Threonine Kinases