The past, present and future of PKMZ in memory
Francis Crick once posed an important question- “How then is memory stored in the brain so that its trace is relatively immune to molecular turnover?” (Glanzman, 2012). Ever since, neuroscientists have been struggling to answer Crick’s question. Long- Term Potentiation (LTP) of synaptic strength is the underlying mechanism for formation of memory. In brief, LTP involves the increase in number of AMPA receptor and its permeability when neurotransmitters bind to NMDA receptor, which allows calcium influx and subsequent activation of Calcium/Calmodulin-dependent protein kinase II (CAMKII). However, the molecular mediators of LTP were only important in the formation of memory, but not the maintenance of it (Sacktor, 2011). Protein Kinase M- Zeta (PKM-ζ) was brought to the spotlight when it was first identified as the molecule responsible for maintaining long- term memory (Sacktor et al., 1993). This prompted a plethora of studies hoping to derive the mechanism of PKM-ζ. Only recently, a few emerging publications are suggesting that PKM-ζ do not play any role in memory. I will be reviewing a publication that supports PKM-ζ and one that disprove the roles of PKM-ζ in memory.
PKM-ζ is a key molecule in retaining memory
Early researches have showed that PKM-ζ plays a vital part in maintaining late LTP, a phase requiring gene transcription and mRNA translation, which results in an increased number of AMPA receptors (Derkach et al., 2007). Unlike conventional protein kinases, once PKM-ζ are formed and phosphorylated, it will be constantly active thus, believed to be responsible for maintenance of LTP (King et al., 2012). Although Sacktor et al. first documented the involvement of PKM-ζ ...
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...long-term potentiation. Proceedings of the National Academy of Sciences, 90(18), 8342-8346.
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Volk, L. J., Bachman, J. L., Johnson, R., Yu, Y., & Huganir, R. L. (2013). PKM-[zgr] is not required for hippocampal synaptic plasticity, learning and memory. Nature, 493(7432), 420-423.