LRRK2 Affects Vesicle Trafficking, Neurotransmitter Extracellular Level and Membrane Receptor Localization

被引：60

作者：

Migheli, Rossana ^{[1
]}

Del Giudice, Maria Grazia ^{[2
]}

Spissu, Ylenia ^{[1
]}

Sanna, Giovanna ^{[2
]}

Xiong, Yulan ^{[3
,4
]}

Dawson, Ted M. ^{[3
,4
,5
,7
]}

Dawson, Valina L. ^{[3
,4
,5
,6
,7
]}

Galioto, Manuela ^{[2
]}

Rocchitta, Gaia ^{[1
]}

Biosa, Alice ^{[1
]}

Serra, Pier Andrea ^{[1
]}

Carri, Maria Teresa ^{[8
,9
]}

Crosio, Claudia ^{[2
,8
]}

Iaccarino, Ciro ^{[2
,8
]}

机构：

[1] Univ Sassari, Dept Clin & Expt Med, I-07100 Sassari, Italy

[2] Univ Sassari, Dept Biomed Sci, I-07100 Sassari, Italy

[3] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Neuroregenerat Program, Baltimore, MD USA

[4] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Stem Cell Program, Baltimore, MD USA

[5] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA

[6] Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA

[7] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD USA

[8] IRCCS, Fdn Santa Lucia, Rome, Italy

[9] Univ Roma Tor Vergata, Dept Biol, I-00173 Rome, Italy

来源：

PLOS ONE | 2013年 / 8卷 / 10期

基金：

美国国家卫生研究院;

关键词：

OXIDE/CYCLIC GMP PATHWAY; MICRODIALYSIS IN-VITRO; PARKINSONS-DISEASE; PC12; CELLS; KINASE-ACTIVITY; PLEOMORPHIC PATHOLOGY; DOPAMINE SECRETION; MUTANT LRRK2; PHOSPHORYLATION; ENDOCYTOSIS;

D O I：

10.1371/journal.pone.0077198

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The leucine-rich repeat kinase 2 (LRRK2) gene was found to play a role in the pathogenesis of both familial and sporadic Parkinson's disease (PD). LRRK2 encodes a large multi-domain protein that is expressed in different tissues. To date, the physiological and pathological functions of LRRK2 are not clearly defined. In this study we have explored the role of LRRK2 in controlling vesicle trafficking in different cellular or animal models and using various readouts. In neuronal cells, the presence of LRRK2(G2019S) pathological mutant determines increased extracellular dopamine levels either under basal conditions or upon nicotine stimulation. Moreover, mutant LRRK2 affects the levels of dopamine receptor D1 on the membrane surface in neuronal cells or animal models. Ultrastructural analysis of PC12-derived cells expressing mutant LRRK2(G2019S) shows an altered intracellular vesicle distribution. Taken together, our results point to the key role of LRRK2 to control vesicle trafficking in neuronal cells.

引用

页数：13

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