Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan; Department of Physiology, St. Marianna University School of Medicine, 216-8511, Kanagawa, Japan.
Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan.
Neurosci Res. 2021 Jun;167:38-46. doi: 10.1016/j.neures.2021.03.011. Epub 2021 Apr 15.
Lysosomes are organelles that support diverse cellular functions such as terminal degradation of macromolecules and nutrient recycling. Additionally, lysosomes can fuse with the plasma membrane, a phenomenon referred to as lysosomal exocytosis, to release their contents, including hydrolytic enzymes and cargo proteins. Recently, neuronal activity has been shown to induce lysosomal exocytosis in dendrites and axons. Secreted lysosomal enzyme cathepsin B induces and stabilizes synaptic structural changes by degrading the local extracellular matrix. Extracellular matrix reorganization could also enhance the lateral diffusion of the co-released synaptic organizer Cbln1 along the surface of axons to facilitate new synapse formation. Similarly, lateral diffusion of dendritic AMPA-type glutamate receptors could be facilitated to enhance functional synaptic plasticity. Therefore, lysosomal exocytosis is a powerful way of building new cellular structures through the coordinated destruction of the old environment. Understanding the mechanisms by which lysosomal exocytosis is regulated in neurons is expected to lead to the development of new therapeutics for neuronal plasticity following spinal cord injury or neurodegenerative disease.
溶酶体是支持多种细胞功能的细胞器，如大分子的终末降解和营养物质的回收。此外，溶酶体可以与质膜融合，这一现象称为溶酶体胞吐作用，以释放其内容物，包括水解酶和货物蛋白。最近，神经元活动被证明可以诱导树突和轴突中的溶酶体胞吐作用。分泌的溶酶体酶组织蛋白酶 B 通过降解局部细胞外基质来诱导和稳定突触结构变化。细胞外基质的重组也可以增强共同释放的突触组织者 Cbln1 在轴突表面的侧向扩散，以促进新的突触形成。同样，树突状 AMPA 型谷氨酸受体的侧向扩散也可以得到促进，从而增强功能突触可塑性。因此，溶酶体胞吐作用是一种通过协调破坏旧环境来构建新细胞结构的有力方式。了解神经元中溶酶体胞吐作用的调节机制有望为脊髓损伤或神经退行性疾病后神经元可塑性的治疗提供新的方法。
