Myo3A, One of Two Class III Myosin Genes Expressed in Vertebrate Retina, Is Localized to the Calycal Processes of Rod and Cone Photoreceptors and Is Expressed in the Sacculus

Abstract

The striped bass has two retina-expressed class III myosin genes, each composed of a kinase, motor, and tail domain. We report the cloning, sequence analysis, and expression patterns of the long (Myo3A) and short (Myo3B) class III myosins, as well as cellular localization and biochemical characterization of the long isoform, Myo3A. Myo3A (209 kDa) is expressed in the retina, brain, testis, and sacculus, and Myo3B (155 kDa) is expressed in the retina, intestine, and testis. The tails of these two isoforms contain two highly conserved domains, 3THDI and 3THDII. Whereas Myo3B has three IQ motifs, Myo3A has nine IQ motifs, four in its neck and five in its tail domain. Myo3A localizes to actin filament bundles of photoreceptors and is concentrated in the calycal processes. An anti-Myo3A antibody decorates the actin cytoskeleton of rod inner/outer segments, and this labeling is reduced by the presence of ATP. The ATP-sensitive actin association is a feature characteristic of myosin motors. The numerous IQ motifs may play a structural or signaling role in the Myo3A, and its localization to calycal processes indicates that this myosin mediates a local function at this site in vertebrate photoreceptors. INTRODUCTIONThe asymmetrical shapes of the rods and cones of the vertebrate retina are specialized to mediate photon detection and signal transmission. At the distal ends are the outer segments, which are composed of stacks of photopigmentbearing membranous disks surrounded by the plasma membrane. Progressively proximal to the outer segment are the mitochondrion-packed ellipsoid, the endoplasmic reticulum-and Golgi-rich myoid, the perinuclear region, the axon, and the synapse. The outer segment is connected to the rest of the cell by the narrow connecting cilium, through which metabolic fuels and newly synthesized proteins are transported. Although they maintain highly specialized shapes, photoreceptors are not static. Elaborately choreographed morphogenetic movements establish the specialized shapes of photoreceptors during development. Once formed, photoreceptors undergo outer segment turnover throughout life. This turnover is mediated by the daily addition of new disks to the base of the outer segment and the shedding of effete disks from the tip (Young, 1976). Disk addition requires transport of newly synthesized materials from the perinuclear and myoid regions to and through the connecting cilium. More dramatic photoreceptor motility occurs during retinomotor movements of lower vertebrates; light onset induces cone myoids to contract and rod myoids to elongate, whereas dark onset induces opposite movements (Burnside, 1978).Several observations suggest that the actin cytoskeleton plays an important role in photoreceptor motile processes. Photoreceptors are richly endowed with actin filaments deployed in distinct populations and likely to reflect specialized functional roles. Filamentous actin is concentrated in the distal connecting cilium of the outer segment (Chaitin et al., 1984;Wolfrum and Schmitt, 2000) and throu...

PDZD7 is a modifier of retinal disease and a contributor to digenic Usher syndrome

“…To test these possibilities, we examined all coding exons of MYO3A (strong expression in calycal process of retinal photoreceptors; ref. 8) and MYO15A (interacts with the PDZD7 homolog whirlin; ref. 9) by direct sequencing of patient U329-1.…”

Cubozoan jellyfish: an Evo/Devo model for eyes and other sensory systems

“…A functionally important protein overlapping vision and hearing/balance is class III myosin (Dose et al, 2003, Walsh et al, 2002. In Drosophila, the homologous protein, called NINAC, interacts with multiple components to organize the phototransduction machinery into a signaling complex (Wes et al, 1999); NINAC is also responsible for a recessive retinal degeneration in the fly.…”

Myosin 3A Kinase Activity Is Regulated by Phosphorylation of the Kinase Domain Activation Loop

“…Both isoforms are localized to actin bundle-based structures in sensory cells, including the calycal process of photoreceptors (2,6,7) and the stereocilia of inner ear hair cells (8). MYO3A and -3B are proposed to play a role in maintaining the length of the actin-bundled structures (9,10).…”

“…Early studies found that class III myosins are not only expressed in the inner ear and retina but also in brain, intestine, and testes (2). Recently, modifications in the MYO3A gene were found to be associated with bladder and colon cancer and may be a risk factor for anxiety disorders.…”