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Chaperone complex BAG 2– HSC 70 regulates localization of Caenorhabditis elegans leucine‐rich repeat kinase LRK ‐1 to the Golgi
Author(s) -
Fukuzono Takashi,
Pastuhov Strahil Iv.,
Fukushima Okinobu,
Li Chun,
Hattori Ayuna,
Iemura Shunichiro,
Natsume Tohru,
Shibuya Hiroshi,
Hanafusa Hiroshi,
Matsumoto Kunihiro,
Hisamoto Naoki
Publication year - 2016
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12338
Subject(s) - biology , caenorhabditis elegans , golgi apparatus , microbiology and biotechnology , mutant , chaperone (clinical) , phenotype , protein targeting , synaptic vesicle , gene , genetics , vesicle , membrane protein , endoplasmic reticulum , medicine , pathology , membrane
Mutations in LRRK 2 are linked to autosomal dominant forms of Parkinson's disease. We identified two human proteins that bind to LRRK 2: BAG 2 and HSC 70, 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 LRRK 2. 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.