Khvotchev M, Südhof T C
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235, USA.
J Biol Chem. 1998 Jan 23;273(4):2306-11. doi: 10.1074/jbc.273.4.2306.
Phosphatidylinositol phosphates (PIPs) perform central functions in signal transduction and membrane traffic. Synaptojanin is a PIP 5-phosphatase that is expressed in a brain-specific and a ubiquitous splice variants and is thought to constitute the major PIP 5-phosphatase in mammalian brain (Woscholski, R., Finan, P.M., Radley, E., Totty, N.F., Sterling, A.E., Hsuan, J.J., Waterfield, M. D., and Parker, P. J. (1997) J. Biol. Chem. 272, 9625-9628). We now describe synaptojanin 2, a novel isoform of synaptojanin that, similar to synaptojanin 1, contains an N-terminal SAC1-like sequence and a central 5-phosphatase domain but a distinct, unique C-terminal sequence. Transfection studies demonstrated that synaptojanin 2, like synaptojanin 1, is an active PIP phosphatase. An interesting feature of synaptojanin 1 is the presence of a long open reading frame in the 3' region of the brain mRNA that in non-brain tissues is joined to the coding region by alternative splicing, resulting in a shorter synaptojanin 1 form in brain and a longer form in peripheral tissues (Ramjaun, A. R., and McPherson, P. S. (1996) J. Biol. Chem. 271, 24856-24861). Although it exhibits no homology to synaptojanin 1 in this region, synaptojanin 2 also contains an open reading frame in the 3' region that is subject to alternative splicing. Similar to synaptojanin 1, alternative splicing of synaptojanin 2 is tissue-specific and creates a shorter isoform expressed in brain and a longer form in peripheral tissues. The similar alternative splicing of two homologous proteins in a region of non-homology raises the possibility of evolutionary convergence and supports the significance of the variants. Analysis of mRNAs from three brain regions at different developmental stages revealed that alternative splicing of synaptojanin 2 is a developmentally late event, occurring only after the first postnatal week after the generation of neurons and initial synaptogenesis.
磷脂酰肌醇磷酸酯（PIPs）在信号转导和膜运输中发挥核心作用。突触素是一种PIP 5-磷酸酶，以脑特异性和普遍存在的剪接变体形式表达，被认为是哺乳动物脑中主要的PIP 5-磷酸酶（沃肖尔斯基，R.，菲南，P.M.，拉德利，E.，托蒂，N.F.，斯特林，A.E.，宣，J.J.，沃特菲尔德，M.D.，和帕克，P.J.（1997年）《生物化学杂志》272，9625 - 9628）。我们现在描述突触素2，它是突触素的一种新型异构体，与突触素1相似，包含一个N端SAC1样序列和一个中央5-磷酸酶结构域，但有一个独特的C端序列。转染研究表明，突触素2与突触素1一样，是一种活性PIP磷酸酶。突触素1的一个有趣特征是，脑mRNA的3'区域存在一个长开放阅读框，在非脑组织中通过可变剪接与编码区域相连，导致脑中的突触素1形式较短，外周组织中的形式较长（拉姆乔恩，A.R.，和麦克弗森，P.S.（1996年）《生物化学杂志》271，24856 - 24861）。虽然突触素2在该区域与突触素1没有同源性，但它在3'区域也包含一个开放阅读框，该开放阅读框也会发生可变剪接。与突触素1相似，突触素2的可变剪接是组织特异性的，产生一种在脑中表达的较短异构体和一种在外周组织中表达的较长形式。两种同源蛋白在非同源区域的类似可变剪接增加了进化趋同的可能性，并支持了这些变体的重要性。对不同发育阶段三个脑区的mRNA分析表明，突触素2的可变剪接是一个发育后期事件，仅在神经元产生和初始突触形成后的出生后第一周之后发生。
