Expression of palmitoyl protein thioesterase in neurons

被引：60

作者：

Heinonen, O ^{[1
]}

Kyttälä, A

Lehmus, E

Paunio, T

Peltonen, L

Jalanko, A

机构：

[1] Natl Publ Hlth Inst, Dept Human Mol Genet, FIN-00300 Helsinki, Finland

[2] Univ Helsinki, Dept Med Genet, FIN-00014 Helsinki, Finland

[3] Univ Calif Los Angeles, Sch Med, Gonda Ctr, Dept Human Genet, Los Angeles, CA 90024 USA

来源：

MOLECULAR GENETICS AND METABOLISM | 2000年 / 69卷 / 02期

基金：

芬兰科学院;

关键词：

adenovirus vectors; brain; infantile neuronal ceroid lipofuscinoses; palmitoyl protein thioesterase; PC12-cells; primary neurons;

D O I：

10.1006/mgme.2000.2961

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Infantile neuronal ceroid lipofuscinosis (INCL) is a severe neurodegenerative disorder in childhood that is caused by mutations in the gene encoding lysosomal palmitoyl protein thioesterase (PPT). INCL is characterized by massive and selective loss of cortical neurons. Here we have analyzed the intracellular processing and localization of adenovirus-mediated PPT in mouse primary neurons and NGF-induced PC-12 cells. The neuronal processing of PPT was found to be similar to that observed in peripheral cells, and a significant amount of the PPT enzyme was secreted in the primary neurons. Immunofluorescence analysis of the neuronal cells infected with wild-type PPT showed a granular staining pattern in the cell soma and neuronal shafts. Interestingly, PPT was also found in the synaptic ends of the neuronal cells and the staining pattern of the enzyme colocalized to a significant extent with the synaptic markers SV2 and synaptophysin. These in vitro data correspond with the distribution of endogeneous PPT in mouse brain and suggest that PPT may not solely be a lysosomal hydrolase. The specific targeting of PPT into the neuritic shafts and nerve terminals indicates that PPT may be associated with the maintenance of synaptic function. Furthermore, since a substantial amount of PPT is secreted by neurons, it is tempting to speculate that the enzyme could also have an extracellular substrate. (C) 2000 Academic Press.

引用

页码：123 / 129

页数：7

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