Penna Eduardo, Cerciello Angela, Chambery Angela, Russo Rosita, Cernilogar Filippo M, Pedone Emilia Maria, Perrone-Capano Carla, Cappello Silvia, Di Giaimo Rossella, Crispino Marianna
Department of Biology, University of Naples Federico II, Naples, Italy.
Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania "Luigi Vanvitelli", Caserta, Italy.
Front Mol Neurosci. 2019 Aug 16;12:195. doi: 10.3389/fnmol.2019.00195. eCollection 2019.
Cystatin B (CSTB) is a ubiquitous protein belonging to a superfamily of protease inhibitors. CSTB may play a critical role in brain physiology because its mutations cause progressive myoclonic epilepsy-1A (EPM1A), the most common form of progressive myoclonic epilepsy. However, the molecular mechanisms underlying the role of CSTB in the central nervous system (CNS) are largely unknown. To investigate the possible involvement of CSTB in the synaptic plasticity, we analyzed its expression in synaptosomes as a model system in studying the physiology of the synaptic regions of the CNS. We found that CSTB is not only present in the synaptosomes isolated from rat and mouse brain cortex, but also secreted into the medium in a depolarization-controlled manner. In addition, using biorthogonal noncanonical amino acid tagging (BONCAT) procedure, we demonstrated, for the first time, that CSTB is locally synthesized in the synaptosomes. The synaptic localization of CSTB was confirmed in a human 3D model of cortical development, namely cerebral organoids. Altogether, these results suggest that CSTB may play a role in the brain plasticity and open a new perspective in studying the involvement of CSTB deregulation in neurodegenerative and neuropsychiatric diseases.
胱抑素B（CSTB）是一种普遍存在的蛋白质，属于蛋白酶抑制剂超家族。CSTB可能在脑生理学中发挥关键作用，因为其突变会导致进行性肌阵挛癫痫1A（EPM1A），这是进行性肌阵挛癫痫最常见的形式。然而，CSTB在中枢神经系统（CNS）中作用的分子机制在很大程度上尚不清楚。为了研究CSTB可能参与突触可塑性的情况，我们分析了其在突触体中的表达，将其作为研究CNS突触区域生理学的模型系统。我们发现CSTB不仅存在于从大鼠和小鼠大脑皮层分离的突触体中，还以去极化控制的方式分泌到培养基中。此外，使用生物正交非天然氨基酸标记（BONCAT）方法，我们首次证明CSTB在突触体中是局部合成的。CSTB的突触定位在人类皮质发育的3D模型即脑类器官中得到了证实。总之，这些结果表明CSTB可能在脑可塑性中发挥作用，并为研究CSTB失调在神经退行性疾病和神经精神疾病中的作用开辟了新的视角。
