Conventional and Non-Conventional Roles of Non-Muscle Myosin II-Actin in Neuronal Development and Degeneration

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.

Functional Role of Non-Muscle Myosin II in Microglia: An Updated Review

“…In addition to being present in striated and smooth muscle cells, myosins are also abundant in other different cell types, such as granulocytes, platelets, fibroblasts, neurons, and glial cells, where they are involved in a wide variety of cellular functions [5][6][7][8][9]. The different myosin classes modulate actin-based fundamental cellular processes, including vesicle transport, cell migration, cell-substrate interactions, phagocytosis, secretion, endocytosis, exocytosis, intracellular tracking, organelle and plasma membrane morphology, cell adhesion, and maintenance of cortical tension.…”

“…The different myosin classes modulate actin-based fundamental cellular processes, including vesicle transport, cell migration, cell-substrate interactions, phagocytosis, secretion, endocytosis, exocytosis, intracellular tracking, organelle and plasma membrane morphology, cell adhesion, and maintenance of cortical tension. Moreover, classes of myosins found in the nucleus participate in nuclear functions, including transcription, chromatin remodeling, and chromosome movement [7,8,[10][11][12].…”

Proteomic changes in the hippocampus of large mammals after total-body low dose radiation

“…These results, while novel, are also of particular interest since non-muscle myosin proteins, such as NM2A, have been shown to produce different TPM-associated effects in powering cytoskeletal contractions, and have been described as altered in several neurodegenerative processes including AD, PD, ALS and MS [42][43][44]. Furthermore, TPMs have been reported to be involved in various neurodevelopmental aspects [45].…”

Interneuron migration defects during corticogenesis contribute toDyrk1ahaploinsufficiency syndrome pathogenesis via actomyosin dynamics deregulations

“…6b). Then, looking at the expression of genes involved in cytoskeleton remodeling and nucleokinesis in both mutants 57,58 , we found them more significantly downregulated in the Dyrk1a DlxCre/+ mutant forebrains (Table S1; Supplementary Fig. 6c,d).…”

“…d Focused analysis showing the dysregulation affecting DYRK1A, RHOA, ROCK1, other kinases with myosin light and heavy chain coding genes involved in neuronal development in the Dyrk1a Dlx/+ and Dyrk1a +/- brain at E15.5 58 .…”