Flotillin-1 is an evolutionary-conserved memory-related protein up-regulated in implicit and explicit learning paradigms

Abstract

Introduction. Studies of synaptic plasticity using the marine mollusk Aplysia californica as model system have been successfully used to identify proteins involved in learning and memory. The importance of molecular elements regulated by the learning- related neurotransmitter serotonin in Aplysia can then be explored in rodent models and finally tested for their relevance for human physiology and pathology.Materials and methods. Herein, 2-DE gel-based electrophoresis has been used to investigate protein level changes after treatment with serotonin in Aplysia abdominal ganglia.Results. Twenty-one proteins have been found to be regulated by serotonin, and protein level changes of actin depolymerizing factor (ADF), deleted in azoospermia associated protein (DAZAP-1), and Flotillin-1 have been verified by Western blotting.Discussion. Flotillin-1, a member of the flotillin/reggie family of scaffolding proteins, has been previously found to be involved in neuritic branching and synapse formation in hippocampal neurons in vitro. However, its importance for hippocampal- dependent learning and memory in the mouse has not been examined. Here, elevated levels of Flotillin-1 in hippocampal tissue of mice trained in the Morris water maze confirmed the relevance of Flotillin-1 for memory-related processes in a mammalian system. Thus, a translational approach—from invertebrates to rodents—led to the identification of Flotillin-1 as evolutionary-conserved memory-related protein.

Reggie-1 and reggie-2 (flotillins) participate in Rab11a-dependent cargo trafficking, spine synapse formation and LTP-related AMPA receptor (GluA1) surface exposure in mouse hippocampal neurons

“…Another study showed by mass spectrometry that reggies were also upregulated during memory related strengthening of synapses in Aplysia (Monje et al, 2013) and during barrel cortex plasticity (Butko et al, 2013). These studies are consistent with the present results and emphasize the role of reggie in brain function and synaptic plasticity.…”

“…That reggies are involved in important steps of synapse formation and plasticity was suggested by reports showing by mass spectrometry analyses that flotillin-1/reggie-2 is upregulated during learning-related events in Aplysia and during spatial memory formation in the mouse hippocampus (Monje et al, 2013). Flotillin-1/reggie-2 is downregulated in the cortical barrel fields after sensory deprivation (Butko et al, 2013).…”

Neurotransmitters and Memory

“…These are six key steps in the molecular biological delineation of STM and its conversion to LTM both implicit (procedural) and explicit (declarative) memory (Kandel, 2012). Notably, Monje et al (2013) reported that studies of synaptic plasticity using the marine mollusk Aplysia californica as model system have been successfully used to identify proteins involved in learning and memory. The importance of molecular elements regulated by the learning-related neurotransmitter serotonin in Aplysia can then be explored in rodent models and finally tested for their relevance for human physiology and pathology (Monje et al, 2013).…”

“…An important insight provided by PubMed showing that in 1960 two papers were published while in 2012 354 publications appeared, with a peak (370 papers) in 2008. Notably, Monje et al (2013) using a translational approach-from invertebrates to rodents-reported an evolutionaryconserved memory-related protein upregulated in implicit and explicit learning paradigms.…”

“…Notably, Monje et al (2013) reported that studies of synaptic plasticity using the marine mollusk Aplysia californica as model system have been successfully used to identify proteins involved in learning and memory. The importance of molecular elements regulated by the learning-related neurotransmitter serotonin in Aplysia can then be explored in rodent models and finally tested for their relevance for human physiology and pathology (Monje et al, 2013). For instance, Flotillin-1, a member of the flotillin/reggie family of scaffolding proteins, has been previously found to be involved in neuritic branching and synapse formation in hippocampal neurons in vitro.…”