Microtubule motor transport in the delivery of melanosomes to the actin-rich apical domain of the retinal pigment epithelium

Abstract

Melanosomes are motile, light-absorbing organelles that are present in pigment cells of the skin and eye. It has been proposed that melanosome localization, in both skin melanocytes and the retinal pigment epithelium (RPE), involves melanosome capture from microtubule motors by an unconventional myosin, which dynamically tethers the melanosomes to actin filaments. Recent studies with melanocytes have questioned this cooperative capture model. Here, we test the model in RPE cells by imaging melanosomes associated with labeled actin filaments and microtubules, and by investigating the roles of different motor proteins. We found that a deficiency in cytoplasmic dynein phenocopies the lack of myosin-7a, in that melanosomes undergo fewer of the slow myosin-7a-dependent movements and are absent from the RPE apical domain. These results indicate that microtubule-based motility is required for the delivery of melanosomes to the actin-rich apical domain and support a capture mechanism that involves both microtubule and actin motors.

Melanin Transfer in the Epidermis: The Pursuit of Skin Pigmentation Control Mechanisms

“…A recent report suggests that inter-melanosome repulsion based on actin filament dynamics could maintain the spreading of melanosomes throughout the cytoplasm, without the need for microtubule-dependent transport [ 29 ]. Furthermore, another study showed that in retinal pigment epithelium (RPE) cells, microtubule transport is essential for fast long-range transport of melanosomes and that cytoplasmic dynein is indispensable for the passage of these organelles to an actin filament-dependent transport [ 30 ]. Therefore, the debate on this topic is still ongoing, as evidenced by the suggestion for a role of dynein components in melanosome maturation, position, and transfer to neighboring keratinocytes [ 31 ].…”

Loss of Motor Protein MYO1C Causes Rhodopsin Mislocalization and Results in Impaired Visual Function

“…Additionally, myosin-1 motors affect intracellular trafficking; function as tension-sensitive docks, phagocytosis, or tethers; and power membrane deformation [19][20][21][22]. Unconventional myosins are also proposed to be involved in the lightinduced translocation of mitochondria in photoreceptors and in human non-syndromic deafness [23][24][25][26][27][28]. Genetic mutations in myosins that lead to hearing loss have also been associated with retinal degeneration [29][30][31][32][33].…”

Melanin Distribution in Human Skin: Influence of Cytoskeletal, Polarity, and Centrosome-Related Machinery of Stratum basale Keratinocytes

“…Thereafter, melanin matures and accumulates in the apical compartment of the RPE cell. Despite this significant difference with KCs, Jiang et al (2020) have shown how RPE melanosomes move along MTs until they reach the apical, actin-rich, RPE cell domain, a process dependent on motor proteins [ 27 ]. Thereafter, melanin remains for a lifetime, unless aging or disease perturb it.…”