Kato A, Ozawa F, Saitoh Y, Fukazawa Y, Sugiyama H, Inokuchi K
Mitsubishi Kasei Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan.
J Biol Chem. 1998 Sep 11;273(37):23969-75. doi: 10.1074/jbc.273.37.23969.
Vesl-1S (186 amino acids, also called Homer) is a protein containing EVH1- and PDZ-like domains whose expression in the hippocampus is regulated during long term potentiation (LTP), one form of synaptic plasticity thought to underlie memory formation (Kato, A., Ozawa, F., Saitoh, Y., Hirai, K., and Inokuchi, K. (1997) FEBS Lett. 412, 183-189; Brakeman, P. R., Lanahan, A. A., O'Brien, R., Roche, K., Barnes, C. A., Huganir, R. L., and Worley, P. F. (1997) Nature 386, 284-288). Here we report additional members of the Vesl/Homer family of proteins, Vesl-1L and Vesl-2. Vesl-1L (366 amino acids), a splicing variant of Vesl-1S, shares N-terminal 175 amino acids with Vesl-1S and contains additional amino acids at the C terminus. Vesl-2 (354 amino acids) was highly related to Vesl-1L in that both contain EVH1- and PDZ-like domains at the N terminus (86% conservation) and an MCC (mutated in colorectal cancer)-like domain and a leucine zipper at the C terminus. In contrast to vesl-1S, we observed no changes in the levels of vesl-1L and vesl-2 mRNAs during dentate gyrus LTP. All these proteins interacted with metabotropic glutamate receptors (mGluR1 and mGluR5) as well as several hippocampal proteins in vitro. Vesl-1L and Vesl-2, but not Vesl-1S, interacted with each other through the C-terminal portion that was absent in Vesl-1S. Vesl-1L and Vesl-2 may mediate clustering of mGluRs at synaptic junctions. We propose that Vesl-1S may be involved in the structural changes that occur at metabotropic glutamatergic synapses during the maintenance phase of LTP by modulating the redistribution of synaptic components.
Vesl-1S（186个氨基酸，也称为Homer）是一种含有EVH1和PDZ样结构域的蛋白质，其在海马体中的表达在长时程增强（LTP）过程中受到调控，LTP是一种被认为是记忆形成基础的突触可塑性形式（加藤，A.，小泽，F.，斋藤，Y.，平井，K.，及井口，K.（1997年）《欧洲生物化学学会联合会快报》412，183 - 189；布雷克曼，P.R.，拉纳汉，A.A.，奥布赖恩，R.，罗奇，K.，巴恩斯，C.A.，胡加尼尔，R.L.，及沃利，P.F.（1997年）《自然》386，284 - 288）。在此我们报告Vesl/Homer蛋白家族的其他成员，即Vesl-1L和Vesl-2。Vesl-1L（366个氨基酸）是Vesl-1S的剪接变体，与Vesl-1S共享N端的175个氨基酸，并在C端含有额外的氨基酸。Vesl-2（354个氨基酸）与Vesl-1L高度相关，因为二者在N端均含有EVH1和PDZ样结构域（86%的保守性），且在C端含有一个类MCC（在结直肠癌中发生突变）结构域和一个亮氨酸拉链。与Vesl-1S不同，我们观察到在齿状回LTP过程中Vesl-1L和Vesl-2的mRNA水平没有变化。所有这些蛋白质在体外均与代谢型谷氨酸受体（mGluR1和mGluR5）以及几种海马体蛋白相互作用。Vesl-1L和Vesl-2，但不包括Vesl-1S，通过Vesl-1S中不存在的C端部分相互作用。Vesl-1L和Vesl-2可能介导mGluRs在突触连接处的聚集。我们提出，Vesl-1S可能通过调节突触成分的重新分布，参与LTP维持阶段代谢型谷氨酸能突触处发生的结构变化。
