Expression of axonal protein degradation machinery in sympathetic neurons is regulated by nerve growth factor.
Expression of axonal protein degradation machinery in sympathetic neurons is regulated by nerve growth factor.
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DOI：
10.1002/jnr.23041
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发表时间：
2012-08
影响因子：
4.2
通讯作者：
Pierchala, Brian A.
中科院分区：
文献类型：
--
作者：
Frampton, John P.;Guo, Chong;Pierchala, Brian A.
神经元内蛋白质降解和蛋白水解功能的缺陷与许多神经退行性疾病和发育障碍有关。外周神经元的区隔培养用于研究交感和感觉神经元轴突和细胞体中蛋白水解机制的特性和相对丰度。轴突蛋白免疫印迹显示，LAMP2、LC3和PSMA2在轴突中丰富，表明溶酶体、自噬体和蛋白酶体位于轴突中。有趣的是，通过神经生长因子刺激交感神经元远端轴突，轴突中溶酶体和蛋白酶体相关蛋白的表达选择性上调，这表明轴突的生长和维持需要局部蛋白周转。神经生长因子对轴突中蛋白酶体和溶酶体丰度的调节提供了蛋白质降解与周围神经元营养状态之间的联系。抑制位于轴突的蛋白酶体导致这些轴突中泛素化蛋白的积累。相反，轴突的溶酶体抑制不会导致泛素化蛋白或转铁蛋白受体（一种被溶酶体降解的跨膜蛋白）的积累。有趣的是，溶酶体可以逆行或顺行运输，因此，通常由轴突溶酶体降解的泛素化蛋白很可能被运输到细胞体进行降解。总之，蛋白酶体降解发生在局部，而被溶酶体降解的蛋白质很可能在轴突局部降解，或者被运输到细胞体降解。
Deficiencies in protein degradation and proteolytic function within neurons are linked to a number of neurodegenerative diseases and developmental disorders. Compartmentalized cultures of peripheral neurons were used to investigate the properties and relative abundance of the proteolytic machinery in the axons and cell bodies of sympathetic and sensory neurons. Immunoblotting of axonal proteins demonstrated that LAMP2, LC3 and PSMA2 were abundant in axons, suggesting that lysosomes, autophagosomes and proteasomes were located in axons. Interestingly, the expression of proteins associated with lysosomes and proteasomes were upregulated selectively in axons by NGF stimulation of the distal axons of sympathetic neurons, suggesting that axonal growth and maintenance requires local protein turnover. The regulation of the abundance of both proteasomes and lysosomes in axons by NGF provides a link between protein degradation and the trophic status of peripheral neurons. Inhibition of proteasomes located in axons resulted in an accumulation of ubiquitinated proteins in these axons. In contrast, lysosome inhibition in axons did not result in an accumulation of ubiquitinated proteins or the transferrin receptor, a transmembrane protein degraded by lysosomes. Interestingly, lysosomes were transported both retrogradely and anterogradely, therefore it is likely that ubiquitinated proteins that are normally destined for degradation by lysosomes in axons can be transported to the cell bodies for degradation. In summary, proteasomal degradation occurs locally, whereas proteins degraded by lysosomes can most likely either be degraded locally in axons, or be transported to cell bodies for degradation.
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DOI：
10.1523/jneurosci.6412-10.2011
发表时间：
2011-05-25
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Lee S;Sato Y;Nixon RA
通讯作者：
Nixon RA
影响因子：
14.8
作者：
Campenot, Robert B.;Lund, Karen;Mok, Sue-Ann
通讯作者：
Mok, Sue-Ann
影响因子：
64.8
作者：
Bingol, Baris;Schuman, Erin M.
通讯作者：
Schuman, Erin M.
影响因子：
56.9
作者：
CHAU, V;TOBIAS, JW;VARSHAVSKY, A
通讯作者：
VARSHAVSKY, A
影响因子：
2.9
作者：
GOEDERT, M;OTTEN, U;THOENEN, H
通讯作者：
THOENEN, H