Does PKM(zeta) maintain memory?

Work on the long-term stability of memory has identified a potentially critical role for protein kinase Mzeta (PKM zeta) in maintaining established memory. PKM zeta, an autonomously active isoform of PKC, is hypothesized to sustain those changes that occurred during memory formation in order to preserve the memory engram over time. Initial studies investigating the role of PKM zeta were largely successful in demonstrating a role for the kinase in memory maintenance; disrupting PKM zeta activity with zeta-inhibitory peptide (ZIP) was successful in disrupting a variety of established associations in a number of key brain regions. More recent work, however, has questioned both the role of PKM zeta in memory maintenance and the effectiveness of ZIP as a specific inhibitor of PKM zeta activity. Here, we outline the research both for and against the idea that PKM zeta is a memory maintenance mechanism and discuss how these two lines of research can be reconciled. We conclude by proposing a number of studies that would help to clarify the role of PKM zeta in memory and define other mechanisms the brain may use to maintain memory. (C) 2013 Elsevier Inc. All rights reserved.