Abstract
Myosins are motor proteins that use chemical energy to produce mechanical forces driving actin cytoskeletal dynamics. In the brain, the conventional non-muscle myosin II (NMII) regulates actin filament cytoskeletal assembly and contractile forces during structural remodeling of axons and dendrites, contributing to morphology, polarization, and migration of neurons during brain development. NMII isoforms also participate in neurotransmission and synaptic plasticity by driving actin cytoskeletal dynamics during synaptic vesicle release and retrieval, and formation, maturation, and remodeling of dendritic spines. NMIIs are expressed differentially in cerebral non-neuronal cells, such as microglia, astrocytes, and endothelial cells, wherein they play key functions in inflammation, myelination, and repair. Besides major efforts to understand the physiological functions and regulatory mechanisms of NMIIs in the nervous system, their contributions to brain pathologies are still largely unclear. Nonetheless, genetic mutations or deregulation of NMII and its regulatory effectors are linked to autism, schizophrenia, intellectual disability, and neurodegeneration, indicating non-conventional roles of NMIIs in cellular mechanisms underlying neurodevelopmental and neurodegenerative disorders. Here, we summarize the emerging biological roles of NMIIs in the brain, and discuss how actomyosin signaling contributes to dysfunction of neurons and glial cells in the context of neurological disorders. This knowledge is relevant for a deep understanding of NMIIs on the pathogenesis and therapeutics of neuropsychiatric and neurodegenerative diseases.
Highlights
Myosins are motor proteins that produce tension and contractile forces for movement and sliding of actin filaments in the majority of cells of human tissues
(white) binding sites, followed by an isoleucine-glutamine (IQ) neck region bound to the essential light chains (ELC) and regulatory light chains (RLC), and coiled-coil tail region consisting of a heavy chain (HC) that ends with a non-helical tail region at the C-terminal that defines the subcellular localization
Considering that PAK3 regulates synapse formation and plasticity [155], this result suggests that disruption of synaptic non-muscle myosin II (NMII)/actin could contribute to early synapse dysfunction and cognitive impairment in these diseases
Summary
Myosins are motor proteins that produce tension and contractile forces for movement and sliding of actin filaments in the majority of cells of human tissues. Other kinases mediate RLC phosphorylation at Thr 18 and/or Ser 19, including citron Rho-interacting kinase (CRIK), death-associated protein kinase (DAPK3), myotonic dystrophy-related Cdc42-binding protein kinase (MRCK), serine/threonine-protein kinase 21 (STK21), p-21 activated kinase (PAK), and leucine zipper interacting kinase (ZIPK). The NMII holoenzyme consists of a globular head motor domain at the N-terminal, containing the actin (yellow) and Mg2+ -ATP (white) binding sites, followed by an isoleucine-glutamine (IQ) neck region bound to the essential light chains (ELC) and regulatory light chains (RLC), and coiled-coil tail region consisting of a heavy chain (HC) that ends with a non-helical tail region at the C-terminal that defines the subcellular localization. We discuss the function of actomyosin signaling in neuronal morphology, polarization, migration, and plasticity, and its involvement in neuron dysfunction and death in the context of cognitive and behavioral alterations in neuropsychiatric and neurodegenerative diseases
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
