Abstract
Actin-depolymerization factor (ADF)/cofilin, a family of actin-binding proteins, are critical for the regulation of actin reorganization in response to various signals. Accumulating evidence indicates that ADF/cofilin also play important roles in neuronal structure and function, including long-term potentiation and depression. These are the most extensively studied forms of long-lasting synaptic plasticity and are widely regarded as cellular mechanisms underlying learning and memory. ADF/cofilin regulate synaptic function through their effects on dendritic spines and the trafficking of glutamate receptors, the principal mediator of excitatory synaptic transmission in vertebrates. Regulation of ADF/cofilin involves various signaling pathways converging on LIM domain kinases and slingshot phosphatases, which phosphorylate/inactivate and dephosphorylate/activate ADF/cofilin, respectively. Actin-depolymerization factor/cofilin activity is also regulated by other actin-binding proteins, activity-dependent subcellular distribution and protein translation. Abnormalities in ADF/cofilin have been associated with several neurodegenerative disorders such as Alzheimer’s disease. Therefore, investigating the roles of ADF/cofilin in the brain is not only important for understanding the fundamental processes governing neuronal structure and function, but also may provide potential therapeutic strategies to treat brain disorders.
Highlights
Long-lasting changes in the efficacy of synaptic transmission, including long-term potentiation (LTP) and depression (LTD), are widely regarded as the key mechanisms underlying memory storage (Bliss and Collingridge, 1993; Malenka and Bear, 2004; Citri and Malenka, 2008; Neves et al, 2008; Kessels and Malinow, 2009; Kandel et al, 2014; Mateos-Aparicio and Rodríguez-Moreno, 2019)
Several studies have shown that actin-depolymerization factor (ADF)/cofilin play an important role in the regulating trafficking and accumulation of AMPA receptors within synapses during LTP and this process appears to be distinct from its role in spine morphological plasticity (Gu et al, 2010; Rust et al, 2010)
ADF/cofilin phosphorylation mediated by the activation of the Rho GTPase-PAK/ROCK-LIM domain containing kinase (LIMK) pathway is a key mechanism that is responsible for ADF/cofilin inactivation, actin assembly and spine enlargement during LTP
Summary
Long-lasting changes in the efficacy of synaptic transmission, including long-term potentiation (LTP) and depression (LTD), are widely regarded as the key mechanisms underlying memory storage (Bliss and Collingridge, 1993; Malenka and Bear, 2004; Citri and Malenka, 2008; Neves et al, 2008; Kessels and Malinow, 2009; Kandel et al, 2014; Mateos-Aparicio and Rodríguez-Moreno, 2019). In this review we will focus on the role of actin-depolymerization factor (ADF)/cofilin in the regulation of LTP, LTD, dendritic spines and their dysfunction in Alzheimer’s disease (AD). A study using single-filament approach based on microfluidics suggests that ADF/cofilin-induced actin disassembly is mediated by both severing and depolymerization activity (Wioland et al, 2017).
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