Neurodegenerative and Repair Unit, School of Medical Science, UNSW Sydney, Sydney, NSW, Australia.
Neuron Culture Core Facility (NCCF), University of New South Wales, Sydney, NSW, Australia.
Cell Mol Neurobiol. 2018 Nov;38(8):1557-1563. doi: 10.1007/s10571-018-0620-7. Epub 2018 Sep 14.
Overcoming neurite inhibition is integral for restoring neuronal connectivity after CNS injury. Actin dynamics are critical for neurite growth cone formation and extension. The tropomyosin family of proteins is a regarded as master regulator of actin dynamics. This study investigates tropomyosin isoform 3.1 (Tpm3.1) as a potential candidate for overcoming an inhibitory substrate, as it is known to influence neurite branching and outgrowth. We designed a microfluidic device that enables neurons to be grown adjacent to an inhibitory substrate, Nogo-66. Results show that neurons, overexpressing hTpm3.1, have an increased propensity to overcome Nogo-66 inhibition. We propose Tpm3.1 as a potential target for promoting neurite growth in an inhibitory environment in the central nervous system.
克服神经突抑制对于中枢神经系统损伤后恢复神经元连接至关重要。肌动蛋白动力学对于神经突生长锥的形成和延伸至关重要。原肌球蛋白蛋白家族被认为是肌动蛋白动力学的主要调节因子。本研究将原肌球蛋白异构体 3.1（Tpm3.1）作为克服抑制性底物的潜在候选物进行研究，因为已知它会影响神经突分支和生长。我们设计了一种微流控装置，使神经元能够在抑制性底物 Nogo-66 旁边生长。结果表明，过表达 hTpm3.1 的神经元更有可能克服 Nogo-66 的抑制。我们提出 Tpm3.1 作为促进中枢神经系统抑制环境中神经突生长的潜在靶标。
