The localization of UCH-L1(Ubiquitin C-terminaHydrolase-L1) in lipid rafts of neuronal cell

Parkinson's disease(PD) is the progressive neurodegenerative disorder that profoundly affects movement, and is characterized by dopaminergic neuronal loss in the substantia nigra, midbrain. Symtoms of PD are resting tremor, rigidity, postural instability and slowness of movement. Lipid rafts enriched glycosylphosphatidylinositol (GPI)-anchored proteins, glycosphingolipid and cholresterol, are specialized microdomains that play a role in endocytosis, exocytosis, signal transduction and receptor traffic king. The disruption of lipid raft from alteration of gangliosides and cholesterol content has been reported to cause neurodegenerative disorders such as Alzheimer's disease(AD), Parkinson's disease(PD), Huntington's disease(HD) and Prion's disease and it has been reported that PD-associated genes such as α-synuclein, LRRK2, PINK1,Parkin and DJ-1 as well as AD-associated gene, amyloid-β, Prion's disease-associated gene, prion and HD-associated gene, huntingtin may play important roles in lipid rafts. The functional alteration of lipid rafts by these proteins may be one of common pathological mechanism of PD. PD-associated UCH-L1 gene has been reported to be localized in the plasma membrane and ER membrane. Therefore, in the present study, we obseved that UCH-L1 was also localized in lipid rafts using the sucrose gradient centrifugation assay and soluble-in soluble fractionation assay with cold 1% Triton X-100 buffer in neuronal cell. The results showed that UCH-L1 assoicated with lipid rafts of neuronal cells. And then, we investigated whether the post-translational modifications including palmitoylation, fesylation, dimerization, glycosylation, serine/threonine phosphorylation or tyrosine-phosphorylation play arolein the localization of UCH-L1 into lipid rafts. This study demonstrated that UCH-L1 associated with lipid rafts through tyrosine phosphorylation. But, the tyrosine phosphorylation of UCH-L1 might not affecton its loclization of lipid rafts directly. The localization of UCH-L1 into lipid raft through the tyrosine phosphorylation may cause alteration of signal transduction of lipid rafts. Therefore, I demonstrate that UCH-L1 was localized in lipid rafts of neuronal cell by tyrosine-phosphorylation and suggest that UCH-L1 was related to the functional alteration of lipid rafts with PD-related genes.

Author dc:creator

• 김, 진수

Contributors dc:contributor

• 박, 상면
• 대학원 의생명과학과
• 201224135

• 파킨슨병
• UCH-L1(Ubiquitin C-terminal Hydrolase-L1)
• 지질 래프트
• 타이로신-인산화 반응

Language dc:language

ko

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000017411
000000017411

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/10868