Reiner O, Sapir T
Department of Molecular Genetics, The Weizmann Institute of Science, 76100 Rehovot, Israel.
Int J Mol Med. 1998 May;1(5):849-53. doi: 10.3892/ijmm.1.5.849.
Lissencephaly is a relatively common brain malformation. Lissencephaly type 1 is characterized by the smooth appearance of the cortex and the presence of four abnormally positioned layers instead of the normal six. Lissencephaly is considered to be an abnormality in neuronal migration. The gene mutated in type 1 lissencephaly was cloned by us and designated LIS1. Recently, several genes involved in cortical development have been cloned in the mouse. In human an additional X-linked lissencephaly gene has been identified. We summarize here our current knowledge on the LIS1 gene and its function. It has been identified as a non-catalytic subunit of PAF-acetylhydrolase, a heterotrimeric enzyme which inactivates the platelet-activating factor (PAF). In addition, we have demonstrated that LIS1 interacts with tubulin, and affects the dynamics properties of microtubles. LIS1 contains seven WD repeats and may structurally resemble the beta-subunit of heterotrimeric G proteins. Interestingly, the catalytic subunit of PAF-acetylhydrolase was found to resemble the alpha subunit of heterotrimeric G proteins. We raise the possibility that LIS1 is part of an intracellular signaling pathway involved in neuronal migration.
无脑回畸形是一种相对常见的脑畸形。1型无脑回畸形的特征是皮质外观平滑，存在四个异常定位的细胞层，而非正常的六层。无脑回畸形被认为是神经元迁移异常。我们克隆了1型无脑回畸形中发生突变的基因，并将其命名为LIS1。最近，在小鼠中克隆了几个参与皮质发育的基因。在人类中，又鉴定出一个X连锁的无脑回畸形基因。我们在此总结目前关于LIS1基因及其功能的知识。它已被鉴定为PAF-乙酰水解酶的非催化亚基，PAF-乙酰水解酶是一种使血小板活化因子（PAF）失活的异源三聚体酶。此外，我们已经证明LIS1与微管蛋白相互作用，并影响微管的动力学特性。LIS1包含七个WD重复序列，在结构上可能类似于异源三聚体G蛋白的β亚基。有趣的是，发现PAF-乙酰水解酶的催化亚基类似于异源三聚体G蛋白的α亚基。我们提出LIS1是参与神经元迁移的细胞内信号通路的一部分的可能性。
