| RRC ID |
37021
|
| Author |
Fukuzono T, Pastuhov SI, Fukushima O, Li C, Hattori A, Iemura S, Natsume T, Shibuya H, Hanafusa H, Matsumoto K, Hisamoto N.
|
| Title |
Chaperone complex BAG2-HSC70 regulates localization of Caenorhabditis elegans leucine-rich repeat kinase LRK-1 to the Golgi.
|
| Journal |
Genes Cells
|
| 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.
|
| Volume |
21(4)
|
| Pages |
311-24
|
| Published |
2016-4-1
|
| DOI |
10.1111/gtc.12338
|
| PMID |
26853528
|
| MeSH |
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
|
| IF |
1.655
|
| Times Cited |
5
|
|
WOS Category
|
GENETICS & HEREDITY
CELL BIOLOGY
|
| Resource |
| C.elegans |
tm2899 |
