Role of Protein kinase M (PKM) in maintaining memory

We have shown that distinct PKMs, generated from calpain-mediated cleavage of PKC are required for maintaining distinct forms of synaptic facilitation in Aplysia (Bougie et al, 2012; Farah et al, 2017; Hu et al, 2017a,b). In contrast, work in vertebrates have focused on a single form of PKM generated from an alternative transcript and not calpain cleavage. For non-associative memory in Aplysia, a distinct conserved calpain, the SOL calpain is required for cleaving PKC to PKM and we have generated a SOL conditional KO in mice. We are determining if specific forms of memory are lost in these mice and if these memories require calpain cleavage of other PKCs to PKMs

The memory synapse

We have proposed that synapses that store memories can be distinguished molecularly from other synapses (Sossin, 2018). We are using the Aplysia sensory-motor neuron synapse to test this idea, identifying molecular markers that will predict which synapses will be reversed by compounds that erase memory.

Translational control in learning and memory

We have shown that the major downstream target of TOR in learning in Aplysia is elongation factor 2 kinase (eEF2K; Weatherill et al, 2010; Mchamphill et al, 2017). We are examining how phosphorylation and dephosphorylation of eEF2 can selectively regulate translation of mRNAs important for memory.

mRNAs are transported to synapses in stalled polysomes

We have shown that the majority of ribosomes in hippocampal dendrites are occupied in stalled polysomes (Graber et al, 2013) and that formation of these polysomes require interaction between the RNA binding protein Staufen 2 and the nonsense decay factor UPF1 (Graber et al, 2017). We are continuing to probe the structure and function of these liquid-phase separated organelles and determining their function in health and disease.

The role of calcium-secretion coupling in regulating Transmitter Release

The sensory-motor neuron synapse of Aplysia is an excellent model for understanding how transmitter release is regulated in a physiological manner. Habituation is caused by the loss of release at this synapse, and the animal can regain release after a noxious stimulation through activation of protein kinase C. These changes are mediated by changes in calcium-secretion coupling. We have cloned the major transmitter release calcium channel in Aplysia (Dunn et al, 2018) and are determining how protein-protein interactions with this channel are modified by depression and the reversal of depression