Suchowerska Alexandra K, Fok Sandra, Stefen Holly, Gunning Peter W, Hardeman Edna C, Power John, Fath Thomas
Neurodegeneration and Repair Unit, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
Neuron Culture Core Facility, University of New South Wales, SydneyNSW, Australia.
Front Cell Neurosci. 2017 Dec 22;11:421. doi: 10.3389/fncel.2017.00421. eCollection 2017.
Nerve cell connections, formed in the developing brain of mammals, undergo a well-programmed process of maturation with changes in their molecular composition over time. The major structural element at the post-synaptic specialization is the actin cytoskeleton, which is composed of different populations of functionally distinct actin filaments. Previous studies, using ultrastructural and light imaging techniques have established the presence of different actin filament populations at the post-synaptic site. However, it remains unknown, how these different actin filament populations are defined and how their molecular composition changes over time. In the present study, we have characterized changes in a core component of actin filaments, the tropomyosin (Tpm) family of actin-associated proteins from embryonal stage to the adult stage. Using biochemical fractionation of mouse brain tissue, we identified the tropomyosin Tpm4.2 as the major post-synaptic Tpm. Furthermore, we found age-related differences in the composition of Tpms at the post-synaptic compartment. Our findings will help to guide future studies that aim to define the functional properties of actin filaments at different developmental stages in the mammalian brain.
在哺乳动物发育中的大脑中形成的神经细胞连接,会经历一个程序良好的成熟过程,其分子组成会随时间发生变化。突触后特化的主要结构元件是肌动蛋白细胞骨架,它由功能不同的肌动蛋白丝的不同群体组成。先前使用超微结构和光学成像技术的研究已经确定在突触后位点存在不同的肌动蛋白丝群体。然而,这些不同的肌动蛋白丝群体是如何定义的,以及它们的分子组成如何随时间变化,仍然未知。在本研究中,我们已经表征了从胚胎期到成年期肌动蛋白丝的一个核心成分,即肌动蛋白相关蛋白的原肌球蛋白(Tpm)家族的变化。通过对小鼠脑组织进行生化分级分离,我们确定原肌球蛋白Tpm4.2是主要的突触后Tpm。此外,我们发现突触后区室中Tpm的组成存在与年龄相关的差异。我们的发现将有助于指导未来旨在确定哺乳动物大脑不同发育阶段肌动蛋白丝功能特性的研究。