Interaction of the ERC family of RIM-binding proteins with the liprin-α family of multidomain proteins
Interaction of the ERC family of RIM-binding proteins with the liprin-α family of multidomain proteins
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DOI：
10.1074/jbc.m307561200
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发表时间：
2003-10-24
影响因子：
4.8
通讯作者：
Kim, E
中科院分区：
文献类型：
--
作者：
Ko, J;Na, M;Kim, E
Liprin-alpha/SYD-2是一个多结构域蛋白家族，具有四种已知的同种型。据报道，liprin-alpha的功能之一是调节突触前活动区的发育，但其潜在机制尚不清楚。在这里，我们报告，liprin-alpha直接与ERC（ELKS-Rab 6相互作用蛋白-CAST）蛋白家族相互作用，已知该家族的成员结合RIMs，RIMs是调节神经递质释放的活性区蛋白。体外结果表明，ERC 2/CAST，一种活性区特异性亚型，与所有已知的liprin-alpha亚型相互作用，并且liprin-alpha 1与ERC 2和ERC 1b（ERC 1的剪接变体，分布于胞质和活性区区域）相关。ERC 2在培养的神经元中与liprin-alpha 1共定位，并在脑中与liprin-alpha 1形成复合物。Liprin-alpha 1在培养的神经元中单独表达时，显示出部分突触定位。然而，当与ERC 2共表达时，liprin-alpha 1被重新分布到突触部位。此外，大致上ERC 2的前半部分，其中包含liprin-alpha-binding区域，是足够的liprin-alpha 1的突触定位，而后半部分不是。这些结果表明ERC 2和liprin-alpha之间的相互作用可能参与了liprin-alpha的突触前定位和突触前活动区的分子组织。
Liprin-alpha/SYD-2 is a family of multidomain proteins with four known isoforms. One of the reported functions of liprin-alpha is to regulate the development of presynaptic active zones, but the underlying mechanism is poorly understood. Here we report that liprin-alpha directly interacts with the ERC (ELKS-Rab6-interacting protein-CAST) family of proteins, members of which are known to bind RIMs, the active zone proteins that regulate neurotransmitter release. In vitro results indicate that ERC2/CAST, an active zone-specific isoform, interacts with all of the known isoforms of liprin-alpha and that liprin-alpha1 associates with both ERC2 and ERC1b, a splice variant of ERC1 that distributes to both cytosolic and active zone regions. ERC2 colocalizes with liprin-alpha1 in cultured neurons and forms a complex with liprin-alpha1 in brain. Liprin-alpha1, when expressed alone in cultured neurons, shows a partial synaptic localization. When coexpressed with ERC2, however, liprin-alpha1 is redistributed to synaptic sites. Moreover, roughly the first half of ERC2, which contains the liprin-alpha-binding region, is sufficient for the synaptic localization of liprin-alpha1 while the second half is not. These results suggest that the interaction between ERC2 and liprin-alpha may be involved in the presynaptic localization of liprin-alpha and the molecular organization of presynaptic active zones.