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

了解突触可塑性的分子机制是神经生物学的一个基本目标。突触强度的改变是神经元网络电路中记忆形成的基础，而稳态突触可塑性将神经元的变化维持在生理限度内。我们知道谷氨酸能n -甲基- d -天冬氨酸受体（NMDAR）和α-氨基-3-羟基-5-甲基-4-异恶唑烯丙酸受体（AMPAR）都在突触可塑性的这两种形式中起关键作用。然而，在突触可塑性过程中控制这些受体的分子机制仍有待完全确定。这两种受体的关键调节剂是酪氨酸磷酸酶STEP（纹状体富集磷酸酶），它通过去磷酸化和促进NMDAR和AMPAR的内化来抵消突触强化。虽然我们知道STEP与体内平衡可塑性有关，但维持其作用的分子机制仍有待确定。此外，我们仍然忽略了STEP如何与AMPAR相互作用，这促使我们发现可能代表STEP和AMPAR之间缺失环节的新分子。

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.