Lysophosphatidic acid (LPA) and its receptor, LPA1 , influence embryonic schwann cell migration, myelination, and cell-to-axon segregation.
Lysophosphatidic acid (LPA) and its receptor, LPA1 , influence embryonic schwann cell migration, myelination, and cell-to-axon segregation.
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作者：
Anliker, Brigitte;Choi, Ji Woong;Lin, Mu-En;Gardell, Shannon E.;Rivera, Richard R.;Kennedy, Grace;Chun, Jerold
雪旺细胞（Schwann cell， SC）迁移是周围神经系统髓鞘形成和再髓鞘形成的重要步骤，可由神经调节因子等多肽因子促进。在这里，我们提出了一种脂质因子，溶血磷脂酸（LPA），通过其同源的G蛋白偶联受体（GPCR） LPA1影响SC迁移和外周髓鞘形成的证据。小鼠LPA1零突变体周围神经的超微结构分析显示，sc -轴突分离延迟，单个sc形成多轴突髓鞘，髓鞘变薄。在原代培养中，LPA通过LPA1促进SC迁移，而使用HPLC/MS分析纯化背根神经节神经元的条件培养基支持这些神经元产生LPA。异三聚体g - α蛋白Gαi和小GTPase Rac1被确定为LPA1的重要下游信号成分。这些结果确定了神经元和SC之间的受体介导的LPA信号，通过影响SC轴突分离和髓鞘形成，促进SC迁移并有助于周围神经的正常发育。
Schwann cell (SC) migration is an important step preceding myelination and remyelination in the peripheral nervous system, and can be promoted by peptide factors like neuregulins. Here we present evidence that a lipid factor, lysophosphatidic acid (LPA), influences both SC migration and peripheral myelination through its cognate G protein-coupled receptor (GPCR) known as LPA1. Ultrastructural analyses of peripheral nerves in mouse null-mutants for LPA1 showed delayed SC-to-axon segregation, polyaxonal myelination by single SCs, and thinner myelin sheaths. In primary cultures, LPA promoted SC migration through LPA1, while analysis of conditioned media from purified dorsal root ganglia neurons using HPLC/MS supported the production of LPA by these neurons. The heterotrimeric G-alpha protein, Gαi, and the small GTPase, Rac1, were identified as important downstream signaling components of LPA1. These results identify receptor mediated LPA signaling between neurons and SCs that promote SC migration and contribute to the normal development of peripheral nerves through effects on SC-axon segregation and myelination.
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DOI：
10.1073/pnas.1106129108
发表时间：
2011-09-13
影响因子：
11.1
作者：
Herr, Keira Joann;Herr, Deron R.;Chun, Jerold
通讯作者：
Chun, Jerold
DOI：
10.1083/jcb.135.4.1071
发表时间：
1996-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hecht JH;Weiner JA;Post SR;Chun J
通讯作者：
Chun J
DOI：
10.1073/pnas.97.24.13384
发表时间：
2000-11-21
影响因子：
11.1
作者：
Contos, JJA;Fukushima, N;Chun, J
通讯作者：
Chun, J
影响因子：
4.8
作者：
Li, YW;Gonzalez, MI;Tennekoon, GI
通讯作者：
Tennekoon, GI
DOI：
10.1073/pnas.91.7.2795
发表时间：
1994-03-29
影响因子：
11.1
作者：
ANTON, ES;WESKAMP, G;MATTHEW, WD
通讯作者：
MATTHEW, WD