Membrane palmitoylated protein 2 is a synaptic scaffold protein required for synaptic SK2-containing channel function

Area of Science:

• Neuroscience
• Molecular Biology
• Cell Biology

Background:

• Apamin-sensitive SK2 channels are located in the post-synaptic membrane of mouse CA1 pyramidal neurons.
• These channels are positioned near NMDA-type glutamate receptors and modulate synaptic responses and plasticity.
• Activity- and protein kinase A-dependent trafficking of SK2 channels influences long-term potentiation (LTP).

Purpose of the Study:

• To identify novel synaptic scaffold proteins interacting with SK2-containing channels.
• To investigate the role of MPP2 in the synaptic localization and function of SK2 channels.
• To elucidate the contribution of MPP2-SK2 interactions to synaptic plasticity and LTP.

Main Methods:

• Co-immunoprecipitation and co-purification assays to demonstrate interaction between MPP2 and SK2.
• Analysis of MPP2 expression in post-synaptic densities of CA1 pyramidal neurons.
• siRNA-mediated knockdown of MPP2 to assess its effect on synaptic responses and LTP.

Main Results:

• A novel synaptic scaffold, MPP2 (membrane palmitoylated protein 2), was identified and shown to interact with SK2-containing channels.
• MPP2 is highly expressed in the post-synaptic density of CA1 pyramidal neuron dendritic spines.
• Knockdown of MPP2 abolished SK2 channel function in synaptic responses and reduced LTP induction.

Conclusions:

• MPP2 is a novel synaptic scaffold essential for the proper synaptic localization of SK2-containing channels.
• MPP2 plays a critical role in regulating synaptic transmission and plasticity by mediating SK2 channel function.
• The interaction between MPP2 and SK2 channels is vital for the expression of long-term potentiation.