The Niemann-Pick C1 protein in recycling endosomes of presynaptic nerve terminals

被引:46
作者
Karten, B
Campenot, RB
Vance, DE
Vance, JE [1 ]
机构
[1] Univ Alberta, Canadian Inst Hlth Res, Grp Mol & Cell Biol Lipids, Edmonton, AB T6G 2M7, Canada
[2] Univ Alberta, Dept Med, Edmonton, AB T6G 2M7, Canada
[3] Univ Alberta, Dept Cell Biol, Edmonton, AB T6G 2M7, Canada
[4] Univ Alberta, Dept Biochem, Edmonton, AB T6G 2M7, Canada
关键词
cholesterol; synaptosomes; synaptic vesicles;
D O I
10.1194/jlr.M500482-JLR200
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
Niemann-Pick type C (NPC) disease is a fatal, neurodegenerative disorder caused in 95% of cases by loss of function of NPC1, a ubiquitous endosomal transmembrane protein. A biochemical hallmark of NPC deficiency is cholesterol accumulation in the endocytic pathway. Although cholesterol trafficking defects are observed in all cell types, neurons are the most vulnerable to NPC1 deficiency, suggesting a specialized function for NPC1 in neurons. We investigated the subcellular localization of NPC1 in neurons to gain insight into the mechanism of action of NPC1 in neuronal metabolism. We show that NPC1 is abundant in axons of sympathetic neurons and is present in recycling endosomes in presynaptic nerve terminals. NPC1 deficiency causes morphological and biochemical changes in the presynaptic nerve terminal. Synaptic vesicles from Npc1(-/-) mice have normal cholesterol content but altered protein composition. We propose that NPC1 plays a previously unrecognized role in the presynaptic nerve terminal and that NPC1 deficiency at this site might contribute to the progressive neurological impairment in NPC disease.
引用
收藏
页码:504 / 514
页数:11
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