Abstract
The unconventional myosin VI, a member of the actin-based motor protein family of myosins, is expressed in the retina. Its deletion was previously shown to reduce amplitudes of the a- and b-waves of the electroretinogram. Analyzing wild-type and myosin VI-deficient Snell’s Waltzer mice in more detail, the expression pattern of myosin VI in retinal pigment epithelium, outer limiting membrane, and outer plexiform layer could be linked with differential progressing ocular deficits. These encompassed reduced a-waves and b-waves and disturbed oscillatory potentials in the electroretinogram, photoreceptor cell death, retinal microglia infiltration, and formation of basal laminar deposits. A phenotype comprising features of glaucoma (neurodegeneration) and age-related macular degeneration could thus be uncovered that suggests dysfunction of myosin VI and its variable cargo adaptor proteins for membrane sorting and autophagy, as possible candidate mediators for both disease forms.Electronic supplementary materialThe online version of this article (doi:10.1007/s00018-015-1913-3) contains supplementary material, which is available to authorized users.
Highlights
The unconventional myosin VI, a member of the actinbased myosin motor protein family [1], is a reverse-directed myosin motor that moves towards the minus end of actin filaments [2]
We showed that the presence of myosin VI is essential for maintaining the structural and functional integrity of the mouse retina
The depletion of myosin VI leads to a visual phenotype that may recapitulate functional and morphological characteristics of glaucoma as well as age-related macular degeneration (AMD) pathology
Summary
The unconventional myosin VI, a member of the actinbased myosin motor protein family [1], is a reverse-directed myosin motor that moves towards the minus end of actin filaments [2]. Myosin VI is expressed in many tissues and cell types including hair cells of the cochlea [3] and retinal photoreceptor cells and the retinal pigment epithelium [4, 5]. In hair cells of the cochlea, myosin VI displays dual functions: (1) targeting of protein cargoes to stereocilia, the disturbance of which leads to deafness [6], (2) targeting of cargoes that couple exocytosis and endocytosis, the disturbance of which leads to cell surface shrinkage and disturbed replenishment of vesicles [7, 8]. In the retina of myosin VI-deficient Snell’s Waltzer mice, a-wave and b-wave amplitudes of the electroretinogram (ERG) were found to be reduced, the overall retinal morphology and photoreceptor ultra-structure appeared normal [5]. The details of the pathology behind the reduced amplitudes of the a-wave and b-wave of the ERG described in this myosin VI mutant [5] and another mutant carrying a missense mutation in the motor domain of myosin VI [10] are elusive
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