Abstract
Membrane morphology is an important structural determinant as it reflects cellular functions. The pentaspan membrane protein Prominin-1 (Prom1/CD133) is known to be localised to protrusions and plays a pivotal role in migration and the determination of cellular morphology; however, the underlying mechanism of its action have been elusive. Here, we performed molecular characterisation of Prom1, focussing primarily on its effects on cell morphology. Overexpression of Prom1 in RPE-1 cells triggers multiple, long, cholesterol-enriched fibres, independently of actin and microtubule polymerisation. A five amino acid stretch located at the carboxyl cytosolic region is essential for fibre formation. The small GTPase Rho and its downstream Rho-associated coiled-coil-containing protein kinase (ROCK) are also essential for this process, and active Rho colocalises with Prom1 at the site of initialisation of fibre formation. In mouse embryonic fibroblast (MEF) cells we show that Prom1 is required for chloride ion efflux induced by calcium ion uptake, and demonstrate that fibre formation is closely associated with chloride efflux activity. Collectively, these findings suggest that Prom1 affects cell morphology and contributes to chloride conductance.
Highlights
Membrane morphology is an important structural determinant as it reflects cellular functions
Cell morphology is mainly controlled by the combination of cytoskeletal proteins and the dynamics of plasma membrane curvature and invagination
We found that cell morphology was considerably altered by the overexpression of Prom[1] in a retinal pigmented epithelium derived cell line; numerous long membrane fibres, enriched in cholesterol, were formed
Summary
Membrane morphology is an important structural determinant as it reflects cellular functions. In mouse embryonic fibroblast (MEF) cells we show that Prom[1] is required for chloride ion efflux induced by calcium ion uptake, and demonstrate that fibre formation is closely associated with chloride efflux activity. These findings suggest that Prom[1] affects cell morphology and contributes to chloride conductance. The retinal pigmented epithelium (RPE) cells, localised at the back of the photoreceptor cells, have a unique shape with long protrusions and are assumed to play roles in the photoreceptor disc metabolism[6]. As the knowledge of the molecular characteristics and the signalling pathway(s) induced by Prom[1] is still fragmented, the mechanisms by which the retinal degeneration initiates remain unclear
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