Prominin: A story of cholesterol, plasma membrane protrusions and human pathology

Prominin is the first identified member of a novel family of polytopic memb rane proteins conserved throughout the animal kingdom. It has an unusual me mbrane topology, containing five transmembrane domains and two targe glycos ylated extracellular loops. in mammals, prominin is expressed in Various em bryonic and adult epithelial cells, as well as in nonepithelial cells, such as hematopoietic stem cells. At the subcellular level, prominin is selecti vely localized in microvilli and other plasma membrane protrusions, irrespe ctive of cell type. At the molecular level, prominin specifically interacts with membrane cholesterol and is a marker of a novel type of cholesterol-b ased lipid 'raft'. A frameshift mutation in the human prominin gene, which results in a truncated protein that is no longer transported to the cell su rface, is associated with retinal degeneration. Given that prominin is conc entrated in the plasma membrane evaginations at the base of the outer segme nt of rod photoreceptor cells, which are essential precursor structures in the biogenesis of photoreceptive disks, it is proposed that prominin has a role in the generation of plasma membrane protrusions, their lipid composit ion and organization and their membrane-to-membrane interactions.