Parkin is associated with cellular vesicles

被引:110
作者
Kubo, S
Kitami, T
Noda, S
Shimura, H
Uchiyama, Y
Asakawa, S
Minoshima, S
Shimizu, N
Mizuno, Y
Hattori, N
机构
[1] Juntendo Univ, Sch Med, Dept Neurol, Bunkyo Ku, Tokyo 1138421, Japan
[2] Tokai Univ, Sch Med, Dept Morphol, Kanagawa 2591100, Japan
[3] Osaka Univ, Grad Sch Med, Dept Cell Biol & Neurosci, Osaka, Japan
[4] Keio Univ, Sch Med, Dept Mol Biol, Tokyo, Japan
关键词
AR-JP; autosomal recessive juvenile parkinsonism; Golgi complex; parkin protein; synaptic vesicle; ubiquitin-protein ligase;
D O I
10.1046/j.1471-4159.2001.00364.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We recently identified a novel gene, parkin, as a pathogenic gene for autosomal recessive juvenile parkinsonism. Parkin encodes a 52-kDa protein with a ubiquitin-like domain and two RING-finger motifs. To provide a insight into the function of parkin, we have examined its intracellular distribution in cultured cells. We found that parkin was localized in the trans-Golgi network and the secretory vesicles in U-373MG or SH-SY5Y cells by immunocytochemical analyses. in the subsequent subcellular fractionation studies of rat brain, we showed that parkin was copurified with the synaptic vesicles (SVs) when we used low ionic conditions throughout the procedure. An immunoelectromicroscopic analysis indicated that parkin was present on the SV membrane. Parkin was readily released from SVs into the soluble phase by increasing ionic strength at neutral pH, but not by a non-ionic detergent. To elucidate its responsible region for membrane association, we transfected with green fluorescent protein-tagged deletion mutants of parkin into COS-1 cells followed by subcellular fractionation. We demonstrated the ability of parkin to bind to the membranes through a broad region except for the ubiquitin-like domain. The significance of SV localization of parkin is discussed.
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收藏
页码:42 / 54
页数:13
相关论文
共 58 条
[1]   A wide variety of mutations in the parkin gene are responsible for autosomal recessive parkinsonism in Europe [J].
Abbas, N ;
Lücking, CB ;
Ricard, S ;
Dürr, A ;
Bonifati, V ;
De Michele, G ;
Bouley, S ;
Vaughan, JR ;
Gasser, T ;
Marconi, R ;
Broussolle, E ;
Brefel-Courbon, C ;
Harhangi, BS ;
Oostra, AB ;
Fabrizio, E ;
Böhme, GA ;
Pradier, L ;
Wood, NW ;
Filla, A ;
Meco, G ;
Denefle, P ;
Agid, Y ;
Brice, A .
HUMAN MOLECULAR GENETICS, 1999, 8 (04) :567-574
[2]   STRUCTURAL RELATIONSHIPS BETWEEN CLATHRIN ASSEMBLY PROTEINS FROM THE GOLGI AND THE PLASMA-MEMBRANE [J].
AHLE, S ;
MANN, A ;
EICHELSBACHER, U ;
UNGEWICKELL, E .
EMBO JOURNAL, 1988, 7 (04) :919-929
[3]   Ubiquitin, cellular inclusions and their role in neurodegeneration [J].
Alves-Rodrigues, A ;
Gregori, L ;
Figueiredo-Pereira, ME .
TRENDS IN NEUROSCIENCES, 1998, 21 (12) :516-520
[4]   BIOGENESIS OF SECRETORY GRANULES AND SYNAPTIC VESICLES - FACTS AND HYPOTHESES [J].
BAUERFEIND, R ;
OHASHI, M ;
HUTTNER, WB .
MOLECULAR AND CELL BIOLOGICAL ASPECTS OF GASTROENTEROPANCREATIC NEUROENDOCRINE TUMOR DISEASE, 1994, 733 :233-244
[5]   Degradation of α-synuclein by proteasome [J].
Bennett, MC ;
Bishop, JF ;
Leng, Y ;
Chock, PB ;
Chase, TN ;
Mouradian, MM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (48) :33855-33858
[6]   Degradation of subunits of the Sec61p complex, an integral component of the ER membrane, by the ubiquitin-proteasome pathway [J].
Biederer, T ;
Volkwein, C ;
Sommer, T .
EMBO JOURNAL, 1996, 15 (09) :2069-2076
[7]  
BIEDLER JL, 1978, CANCER RES, V38, P3751
[8]   SCF and cullin/RING H2-based ubiquitin ligases [J].
Deshaies, RJ .
ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, 1999, 15 :435-467
[9]  
Efthimiopoulos S, 1998, J NEUROCHEM, V71, P2365
[10]   A chromosome 4p haplotype segregating with Parkinson's disease and postural tremor [J].
Farrer, M ;
Gwinn-Hardy, K ;
Muenter, M ;
DeVrieze, FW ;
Crook, R ;
Perez-Tur, J ;
Lincoln, S ;
Maraganore, D ;
Adler, C ;
Newman, S ;
MacElwee, K ;
McCarthy, P ;
Miller, C ;
Waters, C ;
Hardy, J .
HUMAN MOLECULAR GENETICS, 1999, 8 (01) :81-85