Neuroligin-1 as a new molecular substrate of the phosphatase STEP, and its involvement in homeostatic synaptic plasticity and memory function

Neuroligin-1作为磷酸酶STEP的新分子底物及其参与稳态突触可塑性和记忆功能

• 批准号: RGPIN-2016-05504
• 负责人: Brouillette, Jonathan
• 金额: $ 2.26万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629445
• 关键词: Neuroligin; new; molecular; substrate; phosphatase

Understanding the molecular mechanisms underlying synaptic plasticity is a fundamental goal in neurobiology. Alteration in synaptic strength underlies memory formation in the neuronal network circuitry, whereas homeostatic synaptic plasticity maintains neuronal changes within physiological limit. We know that the glutamatergic N-methyl-D-aspartate receptor (NMDAR) and α-amino-3-hydroxyle-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) are both critically involved in both forms of synaptic plasticity. However, the molecular mechanisms controlling these receptors during synaptic plasticity still need to be fully established. A key modulator of both receptors is the tyrosine phosphatase STEP (STriatal Enriched Phosphatase) that counteract synaptic strengthening by dephosphorylating and promoting internalization of the NMDAR and AMPAR. Although we know that STEP is involved in homeostatic plasticity, the molecular mechanisms sustaining its action remain to be established. Moreover, we still ignore how STEP interacts with the AMPAR, which prompts us to uncover novel molecules that might represent the missing link between STEP and AMPAR.

了解突触可塑性的分子机制是神经生物学的基本目标。突触强度的改变是神经元网络回路记忆形成的基础，而稳态突触可塑性将神经元的变化维持在生理范围内。我们知道，谷氨酸能N-甲基-D-天冬氨酸受体(NMDAR)和α-amino-3-hydroxyle-5-methyl-4-isoxazolepropionic酸受体(AMPAR)都参与了这两种形式的突触可塑性。然而，在突触可塑性过程中控制这些受体的分子机制仍然需要完全建立。这两种受体的一个关键调节因子是酪氨酸磷酸酶步骤(纹状体富含磷酸酶)，它通过去磷酸化和促进NMDAR和AMPAR的内化来抵消突触增强。虽然我们知道STEP与动态平衡可塑性有关，但维持其作用的分子机制仍有待建立。此外，我们仍然忽略了STEP与AMPAR的相互作用，这促使我们发现了可能代表STEP和AMPAR之间缺失的一环的新分子。