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Prominin-2 is a cholesterol-binding protein associated with apical and basolateral plasmalemmal protrusions in polarized epithelial cells and released into urine

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Abstract

Prominin-2 is a pentaspan membrane glycoprotein structurally related to the cholesterol-binding protein prominin-1, which is expressed in epithelial and non-epithelial cells. Although prominin-1 expression is widespread throughout the organism, the loss of its function solely causes retinal degeneration. The finding that prominin-2 appears to be restricted to epithelial cells, such as those found in kidney tubules, raises the possibility that prominin-2 functionally substitutes prominin-1 in tissues other than the retina and provokes a search for a definition of its morphological and biochemical characteristics. Here, we have investigated, by using MDCK cells as an epithelial cell model, whether prominin-2 shares the biochemical and morphological properties of prominin-1. Interestingly, we have found that, whereas prominin-2 is not restricted to the apical domain like prominin-1 but is distributed in a non-polarized fashion between the apical and basolateral plasma membranes, it retains the main feature of prominin-1, i.e. its selective concentration in plasmalemmal protrusions; prominin-2 is confined to microvilli, cilia and other acetylated tubulin-positive protruding structures. Similar to prominin-1, prominin-2 is partly associated with detergent-resistant membranes in a cholesterol-dependent manner, suggesting its incorporation into membrane microdomains, and binds directly to plasma membrane cholesterol. Finally, prominin-2 is also associated with small membrane particles that are released into the culture media and found in a physiological fluid, i.e. urine. Together, these data show that all the characteristics of prominin-1 are shared by prominin-2, which is in agreement with a possible redundancy in their role as potential organizers of plasma membrane protrusions.

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Correspondence to Denis Corbeil.

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M.F. and N.B. can be considered as joint first authors.

C.T. was supported by the Deutsche Forschungsgemeinschaft (SFB/TR13-04 D2), W.B.H. by the Deutsche Forschungsgemeinschaft (SPP 1109, Hu 275/7-2; SPP 1111, Hu 275/8-2; SFB/TR13-04 B1; SFB 655 A2) and the Fonds der Chemischen Industrie and D.C. was supported by the Deutsche Forschungsgemeinschaft (SPP 1109, CO 298/2-2; SFB/TR13-04 B1; SFB 655 A13) and the Sächsisches Ministerium für Wissenschaft und Kunst: Europäischer Fond für Regionale Entwicklung (4212/05-16).

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Florek, M., Bauer, N., Janich, P. et al. Prominin-2 is a cholesterol-binding protein associated with apical and basolateral plasmalemmal protrusions in polarized epithelial cells and released into urine. Cell Tissue Res 328, 31–47 (2007). https://doi.org/10.1007/s00441-006-0324-z

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