Functions of class V myosins in neurons

Abstract

This minireview focuses on recent studies implicating class V myosins in organelle and macromolecule transport within neurons. These studies reveal that class V myosins play important roles in a wide range of fundamental processes occurring within neurons, including the transport into dendritic spines of organelles that support synaptic plasticity, the establishment of neuronal shape, the specification of polarized cargo transport, and the subcellular localization of mRNA.

Keywords: Cell Polarity; Endoplasmic Reticulum (ER); Ionotropic Glutamate Receptors (AMPA, NMDA); Myosin; Neurons; PTEN; Rab Proteins; Receptor Recycling; Synaptic Plasticity; mRNA.

FIGURE 1.

Structure of myosin Va and its regulation by cargo binding. A, schematic depicting myosin Va, which consists of a pair of heavy chains (blue; N and C termini are indicated) and six calmodulin light chains (yellow) per heavy chain. Each heavy chain harbors a head/motor domain for ATP hydrolysis and actin binding, as well as a neck domain/lever arm with associated calmodulins. The C-terminal tail domain comprises a coiled-coil region for heavy chain dimerization (alternatively spliced exons B, D, and F lead to insertions within this region) and a globular tail domain. Both the globular tail domain and exons D and F have been implicated in cargo binding. The extended, mechanochemically active conformation of cargo-bound myosin V is shown (cargo is indicated in gray). B, schematic of cargo-free myosin Va in its folded conformation. Black arrows indicate that myosin Va is in equilibrium between the folded and extended conformations and that cargo binding leads to myosin Va unfolding and activation. C, myosin Va attached to an actin filament as visualized via electron microscopy followed by image averaging. The image was adapted from Ref. with permission. The head and neck regions are visible. D, myosin Va in its folded conformation as visualized via electron microscopy followed by image averaging. The myosin is shown in the same orientation as in B. The image was adapted from Ref. with permission.

FIGURE 2.

Myosin V functions in neurons. In A, sites of myosin V function are indicated by boxes overlaid on the schematic view of a neuron: red, myosin Va; green, myosin Vb; blue, both isoforms. The letters refer to the physiologic roles attributed to myosin V, which are listed in B. The specific isoform involved is indicated in parentheses in B. AIS, axon initial segment. See text for references.