Vitamin B12 Regulates Glial Migration and Synapse Formation through Isoform-Specific Control of PTP-3/LAR PRTP Expression.
Vitamin B12 Regulates Glial Migration and Synapse Formation through Isoform-Specific Control of PTP-3/LAR PRTP Expression.
复制标题
维生素 B12 通过异构体特异性控制 PTP-3/LAR PRTP 表达来调节神经胶质迁移和突触形成。
DOI：
10.1016/j.celrep.2020.02.113
复制
发表时间：
2020
期刊：
影响因子：
8.8
通讯作者：
Yan,Dong
中科院分区：
文献类型：
--
作者：
Zhang,Albert;Ackley,BrianD;Yan,Dong
众所周知，维生素 B12 在大脑发育和衰老过程中发挥着关键作用，维生素 B12 缺乏与神经发育和退行性疾病有关。然而，维生素 B12 如何影响神经系统发育和维持的潜在分子机制仍不清楚。在此，我们报道维生素 B12 可以通过控制 PTP-3/LAR PRTP（白细胞常见抗原相关受体型酪氨酸蛋白磷酸酶）的亚型特异性表达来调节神经胶质细胞迁移和突触形成。我们发现肠道中饮食提供的维生素 B12 的吸收对于神经元和神经胶质细胞中 PTP-3 (PTP-3A) 长亚型的表达至关重要。 PTP-3A 细胞的表达通过与细胞外基质蛋白 NID-1/nidogen 1 的相互作用自主调节神经胶质细胞迁移和突触形成。 总之，我们的研究结果表明，PTP-3/ LAR PRTP 表达的亚型特异性调节是介导维生素 B12 依赖性神经元和神经胶质细胞发育的关键分子机制。
Vitamin B12 is known to play critical roles during the development and aging of the brain, and vitamin B12 deficiency has been linked to neurodevelopmental and degenerative disorders. However, the underlying molecular mechanisms of how vitamin B12 affects the development and maintenance of the nervous system are still unclear. Here, we report that vitamin B12 can regulate glial migration and synapse formation through control of isoform-specific expression of PTP-3/LAR PRTP (leukocyte-common antigen-related receptor-type tyrosine-protein phosphatase). We found the uptake of diet-supplied vitamin B12 in the intestine to be critical for the expression of a long isoform of PTP-3 (PTP-3A) in neuronal and glial cells. The expression of PTP-3A cell autonomously regulates glial migration and synapse formation through interaction with an extracellular matrix protein NID-1/nidogen 1. Together, our findings demonstrate that isoform-specific regulation of PTP-3/ LAR PRTP expression is a key molecular mechanism that mediates vitamin-B12-dependent neuronal and glial development.