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

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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.