Role of actin cytoskeleton in the organization and function of ionotropic glutamate receptors

Neural networks with precise connection are compulsory for learning and memory. Various cellular events occur during the genesis of dendritic spines to their maturation, synapse formation, stabilization of the synapse, and proper signal transmission. The cortical actin cytoskeleton and its multiple regulatory proteins are crucial for the above cellular events. The different types of ionotropic glutamate receptors (iGluRs) present on the postsynaptic density (PSD) are also essential for learning and memory. Interaction of the iGluRs in association of their auxiliary proteins with actin cytoskeleton regulated by actin-binding proteins (ABPs) are required for precise long-term potentiation (LTP) and long-term depression (LTD). There has been a quest to understand the mechanistic detail of synapse function involving these receptors with dynamic actin cytoskeleton. A major, emerging area of investigation is the relationship between ABPs and iGluRs in synapse development. In this review we have summarized the current understanding of iGluRs functioning with respect to the actin cytoskeleton, scaffolding proteins, and their regulators. The AMPA, NMDA, Delta and Kainate receptors need the stable underlying actin cytoskeleton to anchor through synaptic proteins for precise synapse formation. The different types of ABPs present in neurons play a critical role in dynamizing/stabilizing the actin cytoskeleton needed for iGluRs function.
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Highlights • Interaction of actin cytoskeleton with ionotropic glutamate receptors is prerequisite for memory formation. • Highly remodelled actin cytoskeleton is critical for AMPAR localization and functioning • Calcium influx and Rho GTPases modulate NMDAR activity through LIM kinases. • Delta receptors interacts with various actin-binding proteins like Delphilin, Spectrin, and nPIST. • iGluRs interacts with actin cytoskeleton through ABPs and auxiliary proteins.