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. Author manuscript; available in PMC: 2021 Dec 1.
Published in final edited form as: Biochim Biophys Acta Mol Cell Res. 2020 Aug 27;1867(12):118834. doi: 10.1016/j.bbamcr.2020.118834

Figure 2. Regulation of synaptic SK2 levels and function in synaptic transmission and plasticity.

Figure 2.

A. Synaptic SK2 channels are regulated by PKA phosphorylation and Ube3a ubiquitination; both modifications target SK2 channel for endocytosis. Some of the endocytosed SK2 channels could recycle back to synaptic membranes, while enhanced ubiquitination and phosphorylation target them for degradation in proteasomes, and possibly lysosomes as well. EE, early endosomes; RE, recycling endosomes; LY, lysosomes; Pro, proteasomes. Modified from Sun et al. 2020 (Sun, Liu et al. 2020).

B. SK2 channel-mediated hyperpolarization shunts AMPAR (GluA)-induced depolarization, thereby inhibiting NMDAR (GluN) activation. Removal of SK2 channels by phosphorylation or ubiquitination and inhibition of SK2 channel activity by metabotropic receptors (mGluR1 or M1R) facilitate NMDAR opening and LTP induction. LTP-induced endocytosis of synaptic SK2 channels occurs in parallel with and depends on exocytosis of GluA1-containing AMPARs. The synaptic scaffold protein, MPP2 (membrane palmitoylated protein 2), is crucial for SK2 synaptic localization and function in synaptic plasticity.