Cell Dynamics and Bioimaging Research Center, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea.
PLoS One. 2012;7(4):e34514. doi: 10.1371/journal.pone.0034514. Epub 2012 Apr 4.
Synaptic plasticity is an important feature of neurons essential for learning and memory. Postsynaptic organization and composition are dynamically remodeled in response to diverse synaptic inputs during synaptic plasticity. During this process, the dynamics and localization of postsynaptic proteins are also precisely regulated. NESH/Abi-3 is a member of the Abl interactor (Abi) protein family. Overexpression of NESH is associated with reduced cell motility and tumor metastasis. Strong evidence of a close relationship between NESH and the actin cytoskeleton has been documented. Although earlier studies have shown that NESH is prominently expressed in the brain, its function and characteristics are yet to be established. Data from the present investigation suggest that synaptic localization of NESH in hippocampal neurons is regulated in an F-actin-dependent manner. The dynamic fraction of NESH in the dendritic spine was analyzed using FRAP (fluorescence recovery after photobleaching). Interestingly, F-actin stabilization and disruption significantly affected the mobile fraction of NESH, possibly through altered interactions of NESH with the F-actin. In addition, NESH was synaptically targeted from the dendritic shaft to spine after induction of chemical LTP (long-term potentiation) and the translocation was dependent on F-actin. Our data collectively support the significance of the F-actin cytoskeleton in synaptic targeting of NESH as well as its dynamics.
突触可塑性是神经元的一个重要特征，对于学习和记忆至关重要。在突触可塑性过程中，针对不同的突触输入，突触后组织和组成会发生动态重塑。在此过程中，突触后蛋白的动力学和定位也受到精确调节。NESH/Abi-3 是 Abl 相互作用蛋白 (Abi) 家族的一员。NESH 的过表达与细胞迁移能力降低和肿瘤转移有关。有强有力的证据表明 NESH 与肌动蛋白细胞骨架密切相关。尽管早期的研究表明 NESH 在大脑中表达丰富，但它的功能和特性尚未确定。本研究的数据表明，海马神经元中 NESH 的突触定位受 F-actin 依赖性调节。通过 FRAP（光漂白后荧光恢复）分析 NESH 在树突棘中的动态部分。有趣的是，F-actin 的稳定和破坏显著影响了 NESH 的可动部分，可能是通过改变 NESH 与 F-actin 的相互作用。此外，化学长时程增强（LTP）诱导后，NESH 从树突干向棘突突触定位，易位依赖于 F-actin。我们的数据共同支持了 F-actin 细胞骨架在 NESH 突触定位及其动力学中的重要性。
