Serine/threonine‐protein phosphatase 1 α levels are paralleling olfactory memory formation in the CD1 mouse

Abstract

Although olfactory discrimination has already been studied in several mouse strains, data on protein levels linked to olfactory memory are limited. Wild mouse strains Mus musculus musculus, Mus musculus domesticus and CD1 laboratory outbred mice were tested in a conditioned odor preference task and trained to discriminate between two odors, Rose and Lemon, by pairing one odor with a sugar reward. Six hours following the final test, mice were sacrificed and olfactory bulbs (OB) were taken for gel-based proteomics analyses and immunoblotting. OB proteins were extracted, separated by 2-DE and quantified using specific software (Proteomweaver). Odor-trained mice showed a preference for the previously rewarded odor suggesting that conditioned odor preference occurred. In CD1 mice levels, one out of 482 protein spots was significantly increased in odor-trained mice as compared with the control group; it was in-gel digested by trypsin and chymotrypsin and analyzed by tandem mass spectrometry (nano-ESI-LC-MS/MS). The spot was unambiguously identified as serine/threonine-protein phosphatase PP1-α catalytic subunit (PP-1A) and differential levels observed in gel-based proteomic studies were verified by immunoblotting. PP-1A is a key signalling element in synaptic plasticity and memory processes and is herein shown to be paralleling olfactory discrimination representing olfactory memory.

PP1γ functionally augments the alternative splicing of CaMKIIδ through interaction with ASF

“…Although their homologues are 80% identical in amino sequence, they still exhibit distinct functions. For example, PP1␣ is essential for the formation of synaptic plasticity and memory processes (35); PP1␤ was found to attenuate Ca 2ϩ transients in cardiomyocytes (1); and PP1␥ mediates the striatal dopamine depletion-induced hyperphosphorylation of synaptic proteins in brain (3). However, how these isoforms are involved in cardiac dysfunction is not clear.…”

Perinatal α‐linolenic acid availability alters the expression of genes related to memory and to epigenetic machinery, and the Mecp2 DNA methylation in the whole brain of mouse offspring

“…While the role of the Ppp1cc subunit has not been sufficiently studied in brain, controversial roles have been assigned to the PP1 complex in regard to memory. In CD1 mice, PP1 levels were positively associated with olfactory memory (Winding et al, 2011). In contrast, increased PP1 activity was implicated in deficits in learning and memory induced by lead exposure in postnatal rats (Rahman et al, 2012), and in the epigenetic suppression of fear memory and synaptic plasticity in the amygdala (Koshibu et al, 2011).…”

Rescue of cardiac failing and remodelling by inhibition of protein phosphatase 1γis associated with suppression of the alternative splicing factor-mediated splicing of Ca2+/calmodulin-dependent protein kinase δ

“…Furthermore, the selective interaction between ASF and PP1 isoforms shows a functional diversity for PP1 isoforms in hypertrophic hearts. For example, PP1 α was reported to be essential for the formation of synaptic plasticity and memory processes; PP1 α also stimulates apoptosis of tumour cells by interacting with the retinoblastoma protein; PP1 β was found to attenuate Ca 2+ transients in cardiomyocytes; downregulation of PP1 β can ameliorate left ventricular diastolic function by interrupting the function of sarcoplasmic reticulum Ca 2+ ATPase; PP1 γ was found to mediate the striatal dopamine depletion‐induced hyperphosphorylation of synaptic proteins in brain, and regulate the development of specialized flagellar structures in mammalian spermatozoa by binding to testis leucine rich repeat . The deficiency of the interaction between PP1 α and ASF in cardiac tissues provides an opportunity to explore the function of PP1 α in other tissues, and also prompts us to study the exact reason for the selectivity of PP1 isoforms association with ASF.…”

“…The three isoforms show different functions. For example, PP1 α is essential for the formation of synaptic plasticity and memory processes . PP1 β attenuates Ca 2+ transients in cardiomyocytes .…”