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The Past, Present And Future Of Pkmz In Memory

1280 words - 5 pages

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 in memory during 1993, their actual mechanism has not been clearly understood. In this segment, I will be reviewing an article by Migues et al. “PKM-ζ maintains memories by regulating GluR2-dependent AMPA receptor trafficking (2010)” that demonstrated how PKM-ζ is involved in memory maintenance through regulation of GluR2- dependent AMPA receptor trafficking.

N- terminal truncated PKM-ζ, which is encoded by PRKCZ gene, lacks a regulatory domain and thus, is persistently active. Migues et al. suggested that PKM-ζ regulates NSF/GluR2- dependent AMPA receptor trafficking resulting in a persistent increase number of postsynaptic AMPAR. Migues et al. investigated the effect of PKM-ζ on retrograde and anterograde memory by infusing Zeta Inhibitory Protein (ZIP) into rats’ amygdala. Results showed that trained conditional fear memory was lost in rats but rats retrained after infusion showed normal conditioned- fear responses. This suggests that PKM-ζ is only able to affect memory maintenance but not formation of memory. Next, Migues et al. had to find out how PKM-ζ inhibition affects memory maintenance. By inhibiting GluR2-dependent AMPA receptor removal via GluR23Y, which blocks GluR2- dependent endocytosis (Fig. 1), they...

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