Ca2+ Requirements and Beyond: Signal Transduction in Pigment Granule Motility of Retinal Pigment Epithelium

Johnson, Adam Stephen
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Through the study of melanosome movement many general intracellular motility mechanisms have been discovered. Melanosomes are found in both melanophores and retinal pigment epithelial (RPE) cells. Both cell types possess the ability to respond to chemical agents by either trafficking melanosomes toward the nucleus (aggregation) or down the lengths of distal dendrites or processes ( dispersion). Despite many similarities in regulation of motility, key differences exist between melanophores and RPE. For example, high levels of cAMP are necessary for melanophore dispersion, whereas increased [ cAMP] 1 in RPE cells promotes aggregation. Why similar mechanisms drive different functions remains unclear. In the RPE of bluegill (Lepomis macrochirus), dispersion can be induced by acetylcholine ( or its analog carbachol) binding to Modd muscarinic receptors on the RPE leading to a cascade of messengers ultimately causing pigment granules to move inside long processes among the outer segments of photoreceptors in the retina. In other systems, Modd receptor activation has been shown to be linked to Caz+ mobilization. Therefore, I hypothesized that an elevation in intracellular Caz+ is required for carbacholinduced pigment granule dispersion. In this study I investigated the requirement for Caz+. I found that intracellular, but not extracellular, Caz+ is necessary for carbachol-induced dispersion. This finding supports my hypothesis that an elevation in intracellular Caz+ is required for carbachol-induced pigment granule dispersion. Furthermore, I studied possible calcium-dependent effectors. I found calcineurin and phosphodiesterase-4 to be necessary components of the carbachol-mediated dispersion pathway. Protein kinase C plays a minor role if any.
animals, melanophores, cells, cell physiology, calcium
Johnson, A. S. (2007). Ca2+ requirements and beyond: Signal transduction in pigment granule motility of retinal pigment epithelium (Unpublished thesis). Texas State University-San Marcos, San Marcos, Texas.