237 613

Cited 34 times in

Loss of parkin promotes lipid rafts-dependent endocytosis through accumulating caveolin-1: implications for Parkinson's disease.

Authors
Cha, SH  | Choi, YR | Heo, CH | Kang, SJ | Joe, EH  | Jou, I  | Kim, HM | Park, SM
Citation
Molecular neurodegeneration, 10. : 63-63, 2015
Journal Title
Molecular neurodegeneration
ISSN
1750-1326
Abstract
BACKGROUND: Parkinson's disease (PD) is characterized by progressive loss of midbrain dopaminergic neurons, resulting in motor dysfunctions. While most PD is sporadic in nature, a significant subset can be linked to either autosomal dominant or recessive mutations. PARK2, encoding the E3 ubiquitin ligase, parkin, is the most frequently mutated gene in autosomal recessive early onset PD. It has recently been reported that PD-associated gene products such as PINK1, α-synuclein, LRRK2, and DJ-1, as well as parkin associate with lipid rafts, suggesting that the dysfunction of these proteins in lipid rafts may be a causal factor of PD. Therefore here, we examined the relationship between lipid rafts-related proteins and parkin.

RESULTS: We identified caveolin-1 (cav-1), which is one of the major constituents of lipid rafts at the plasma membrane, as a substrate of parkin. Loss of parkin function was found to disrupt the ubiquitination and degradation of cav-1, resulting in elevated cav-1 protein level in cells. Moreover, the total cholesterol level and membrane fluidity was altered by parkin deficiency, causing dysregulation of lipid rafts-dependent endocytosis. Further, cell-to-cell transmission of α-synuclein was facilitated by parkin deficiency.

CONCLUSIONS: Our results demonstrate that alterations in lipid rafts by the loss of parkin via cav-1 may be a causal factor of PD, and cav-1 may be a novel therapeutic target for PD.
MeSH

DOI
10.1186/s13024-015-0060-5
PMID
26627850
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
Ajou Authors
박, 상면  |  조, 은혜  |  주, 일로  |  차, 선희
Full Text Link
Files in This Item:
26627850.pdfDownload
Export

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse