Mechanisms and Functions of Activity-Regulated Cytoskeleton-Associated Protein in Synaptic Plasticity.

Activity-regulated cytoskeleton-associated protein (Arc) is one of the most important regulators of cognitive functions in the brain regions. As a hub protein, Arc plays different roles in modulating synaptic plasticity. Arc supports the maintenance of long-term potentiation (LTP) by regulating actin cytoskeletal dynamics, while it guides the endocytosis of AMPAR in long-term depression (LTD). Moreover, Arc can self-assemble into capsids, leading to a new way of communicating among neurons. The transcription and translation of the immediate early gene Arc are rigorous procedures guided by numerous factors, and RNA polymerase II (Pol II) is considered to regulate the precise timing dynamics of gene expression. Since astrocytes can secrete brain-derived neurotrophic factor (BDNF) and L-lactate, their unique roles in Arc expression are emphasized. Here, we review the entire process of Arc expression and summarize the factors that can affect Arc expression and function, including noncoding RNAs, transcription factors, and posttranscriptional regulations. We also attempt to review the functional states and mechanisms of Arc in modulating synaptic plasticity. Furthermore, we discuss the recent progress in understanding the roles of Arc in the occurrence of major neurological disorders and provide new thoughts for future research on Arc.