Abstract

Myosin Va functions as a processive, actin-based motor molecule highly enriched in the nervous system, which transports and/or tethers organelles, vesicles, and mRNA and protein translation machinery. Mutation of myosin Va leads to Griscelli disease that is associated with severe neurological deficits and a short life span. Despite playing a critical role in development, the expression of myosin Va in the central nervous system throughout the human life span has not been reported. To address this issue, the cerebellar expression of myosin Va from newborns to elderly humans was studied by immunohistochemistry using an affinity-purified anti-myosin Va antibody. Myosin Va was expressed at all ages from the 10th postnatal day to the 98th year of life, in molecular, Purkinje and granular cerebellar layers. Cerebellar myosin Va expression did not differ essentially in localization or intensity from childhood to old age, except during the postnatal developmental period. Structures resembling granules and climbing fibers in Purkinje cells were deeply stained. In dentate neurons, long processes were deeply stained by anti-myosin Va, as were punctate nuclear structures. During the first postnatal year, myosin Va was differentially expressed in the external granular layer (EGL). In the EGL, proliferating prospective granule cells were not stained by anti-myosin Va antibody. In contrast, premigratory granule cells in the EGL stained moderately. Granule cells exhibiting a migratory profile in the molecular layer were also moderately stained. In conclusion, neuronal myosin Va is developmentally regulated, and appears to be required for cerebellar function from early postnatal life to senescence.

Highlights

  • The myosin superfamily is composed of more than 20 structurally distinct classes of myosins, which are widely expressed in eukaryotes [1]

  • The molecular layer (MOL) exhibited a radial-like staining at all ages (Figure 2B, K, N) that was more pronounced during the first postnatal year (Figure 2N)

  • These demonstrations of the ubiquitous localization of myosin Va to neurons and nervous tissue over a broad phylogenetic range underscore the importance of this molecular motor to fundamental neuronal processes

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Summary

Introduction

The myosin superfamily is composed of more than 20 structurally distinct classes of myosins, which are widely expressed in eukaryotes [1]. Vertebrate class V myosins are two-headed, actin-based processive motors. They convert the chemical energy of ATP hydrolysis to generate force and movement along actin filaments. Class V myosins are involved in intracellular organelle and mRNA transport and signaling [2,3]. Myosin Va [2,5,6] is expressed mainly in neurons, neuroendocrine cells and melanocytes, whereas myosins Vb and Vc are expressed in epithelial cells [7]. In neurons and neuroendocrine cells, myosin Va has been associated with distribution, docking and release of secretory granules

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