Department of Neurobiology, University of Alabama, Birmingham, AL 35294, USA.
J Neurosci. 2011 Jan 26;31(4):1448-60. doi: 10.1523/JNEUROSCI.3294-10.2011.
Ongoing synaptic function and rapid, bidirectional plasticity are both controlled by regulatory mechanisms within dendritic spines. Spine actin dynamics maintain synapse structure and function, and cytoskeletal rearrangements in these structures trigger structural and functional plasticity. Therefore, proteins that interact with actin filaments are attractive candidates to regulate synaptic actin dynamics and, thus, synapse structure and function. Here, we have cloned the rat isoform of class II myosin heavy chain MyH7B in brain. Unexpectedly, this isoform resembles muscle-type myosin II rather than the ubiquitously expressed nonmuscle myosin II isoforms, suggesting that a rich functional diversity of myosin II motors may exist in neurons. Indeed, reducing the expression of MyH7B in mature neurons caused profound alterations to dendritic spine structure and excitatory synaptic strength. Structurally, dendritic spines had large, irregularly shaped heads that contained many filopodia-like protrusions. Neurons with reduced MyH7B expression also had impaired miniature EPSC amplitudes accompanied by a decrease in synaptic AMPA receptors, which was linked to alterations of the actin cytoskeleton. MyH7B-mediated control over spine morphology and synaptic strength was distinct from that of a nonmuscle myosin, myosin IIb. Interestingly, when myosin IIb expression and MyH7B expression were simultaneously knocked-down in neurons, a third, more pronounced phenotype emerged. Together, our data provide evidence that distinct myosin II isoforms work together to regulate synapse structure and function in cultured hippocampal neurons. Thus, myosin II motor activity is emerging as a broad regulatory mechanism for control over complex actin networks within dendritic spines.
树突棘中的调节机制控制着持续的突触功能和快速、双向的可塑性。棘突中的肌动蛋白动力学维持着突触的结构和功能，而这些结构中的细胞骨架重排触发了结构和功能的可塑性。因此，与肌动蛋白丝相互作用的蛋白质是调节突触肌动蛋白动力学的有吸引力的候选物，从而调节突触的结构和功能。在这里，我们在脑中克隆了大鼠 II 型肌球蛋白重链 MyH7B 的同工型。出乎意料的是，这种同工型类似于肌肉型肌球蛋白 II，而不是普遍表达的非肌肉肌球蛋白 II 同工型，这表明神经元中可能存在丰富的肌球蛋白 II 马达的功能多样性。事实上，在成熟神经元中降低 MyH7B 的表达会导致树突棘结构和兴奋性突触强度发生深刻变化。从结构上看，树突棘的头部较大，形状不规则，包含许多类似于丝状伪足的突起。MyH7B 表达减少的神经元还伴有微小 EPSC 幅度的损伤，以及突触 AMPA 受体的减少，这与肌动蛋白细胞骨架的改变有关。MyH7B 介导的对棘突形态和突触强度的控制与非肌球蛋白 II，肌球蛋白 IIb 的控制不同。有趣的是，当神经元中肌球蛋白 IIb 的表达和 MyH7B 的表达同时被敲低时，出现了第三种更为明显的表型。总之，我们的数据提供了证据，表明不同的肌球蛋白 II 同工型共同作用，以调节培养的海马神经元中的突触结构和功能。因此，肌球蛋白 II 马达的活性正在成为调节树突棘内复杂肌动蛋白网络的广泛调节机制。
