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Wnt Secretion and Gradient Formation

Department of Pharmacology and Toxicology, University of Lausanne, Rue du Bugnon 27, Lausanne CH-1005, Switzerland
Institute of Protein Research, Russian Academy of Sciences, Institutskaya 4, Pushchino 142290, Russia
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2013, 14(3), 5130-5145;
Received: 31 January 2013 / Revised: 20 February 2013 / Accepted: 22 February 2013 / Published: 1 March 2013
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells)
Concentration gradients formed by the lipid-modified morphogens of the Wnt family are known for their pivotal roles during embryogenesis and adult tissue homeostasis. Wnt morphogens are also implicated in a variety of human diseases, especially cancer. Therefore, the signaling cascades triggered by Wnts have received considerable attention during recent decades. However, how Wnts are secreted and how concentration gradients are formed remains poorly understood. The use of model organisms such as Drosophila melanogaster has provided important advances in this area. For instance, we have previously shown that the lipid raft-associated reggie/flotillin proteins influence Wnt secretion and spreading in Drosophila. Our work supports the notion that producing cells secrete Wnt molecules in at least two pools: a poorly diffusible one and a reggie/flotillin-dependent highly diffusible pool which allows morphogen spreading over long distances away from its source of production. Here we revise the current views of Wnt secretion and spreading, and propose two models for the role of the reggie/flotillin proteins in these processes: (i) reggies/flotillins regulate the basolateral endocytosis of the poorly diffusible, membrane-bound Wnt pool, which is then sorted and secreted to apical compartments for long-range diffusion, and (ii) lipid rafts organized by reggies/flotillins serve as “dating points” where extracellular Wnt transiently interacts with lipoprotein receptors to allow its capture and further spreading via lipoprotein particles. We further discuss these processes in the context of human breast cancer. A better understanding of these phenomena may be relevant for identification of novel drug targets and therapeutic strategies. View Full-Text
Keywords: Wnt secretion; morphogen; gradient formation; reggie/flotillin proteins; breast cancer; Drosophila Wnt secretion; morphogen; gradient formation; reggie/flotillin proteins; breast cancer; Drosophila
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MDPI and ACS Style

Solis, G.P.; Lüchtenborg, A.-M.; Katanaev, V.L. Wnt Secretion and Gradient Formation. Int. J. Mol. Sci. 2013, 14, 5130-5145.

AMA Style

Solis GP, Lüchtenborg A-M, Katanaev VL. Wnt Secretion and Gradient Formation. International Journal of Molecular Sciences. 2013; 14(3):5130-5145.

Chicago/Turabian Style

Solis, Gonzalo P., Anne-Marie Lüchtenborg, and Vladimir L. Katanaev. 2013. "Wnt Secretion and Gradient Formation" International Journal of Molecular Sciences 14, no. 3: 5130-5145.

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