PTEN regulation of neural development and CNS stem cells
PTEN regulation of neural development and CNS stem cells
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DOI：
10.1002/jcb.10312
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发表时间：
2003-01-01
影响因子：
4
通讯作者：
Ross, AH
中科院分区：
文献类型：
--
作者：
Li, L;Liu, FH;Ross, AH
尽管磷脂酰肌醇被磷脂酰肌醇3-激酶(PI3K)磷酸化在神经系统中起着重要和普遍的作用，但人们对逆转这一反应的磷酸酶知之甚少。这种在10号染色体上缺失的磷酸酶、磷酸酶和张力蛋白同源物(PTEN)被克隆出来，作为胶质瘤的肿瘤抑制因子。PTEN在大多数(如果不是全部)神经元中表达，定位于胞核和胞浆。最近，一系列使用PTEN条件性敲除的论文极大地扩展了我们对PTEN在发育过程中的作用的认识。PTEN的丢失会导致大脑的混乱，可能是由于细胞迁移的缺陷。此外，神经元胞体大小逐渐增大，类似于Lhermitte-Duclos病。我们实验室最近在成年PTEN+/-小鼠身上的实验表明，PTEN调节脑室下区的前体细胞向嗅球的迁移。我们还发现，PTEN单倍体缺陷可以保护前体细胞免受氧化应激诱导的凋亡。总而言之，这些研究表明，PTEN的作用远远不止抑制肿瘤。它是发育和成人大脑的主要调节器。(C)2002年Wiley-Liss，Inc.
Even though phosphorylation of phosphatidylinositols by phosphoinositide 3-kinase (PI3K) has an important and pervasive role in the nervous system, there is little known about the phosphatases that reverse this reaction. Such a phosphatase, phosphatase and tensin homologue deleted on chromosome 10 (PTEN), was cloned as a tumor suppressor for gliomas. PTEN is expressed in most, if not all, neurons and is localized in the nucleus and cytoplasm. Recently, a series of papers using PTEN conditional knockouts has greatly extended our knowledge of PTEN's role during development. Loss of PTEN results in disorganization of the brain, probably due to a flaw in cell migration. In addition, there is a gradual increase in the size of neuronal soma, mimicking Lhermitte-Duclos disease. Recent experiments in our laboratory with adult PTEN +/- mice demonstrate that PTEN regulates migration of precursor cells in the subventricular zone to the olfactory bulb. We also found that PTEN haploinsufficiency can protect precursor cells from apoptosis in response to oxidative stress. Collectively, these studies demonstrate that PTEN does much more than suppressing tumors. It is a master regulator in developing and adult brain. (C) 2002 Wiley-Liss, Inc.