Mammalian Wnt3a is Released on Lipoprotein Particles

• Published in: Traffic (Copenhagen, Denmark) Vol. 10; no. 3; pp. 334 - 343
• Main Authors: Neumann, Sylvia, Coudreuse, Damien Y.M, van der Westhuyzen, Deneys R, Eckhardt, Erik R.M, Korswagen, Hendrik C, Schmitz, Gerd, Sprong, Hein
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.03.2009; Blackwell Publishing Ltd
• Subjects: Animals; Cell Line; Cricetinae; Fatty Acid Transport Proteins - metabolism; lipid modification; lipoprotein receptors; lipoproteins; Lipoproteins - metabolism; signaling; Wnt Proteins - genetics; Wnt Proteins - metabolism; Wnt3 Protein; Wnt3a; Wnt3A Protein
• ISSN: 1398-9219; 1600-0854
• DOI: 10.1111/j.1600-0854.2008.00872.x

Little is known about the release and intercellular transport of Wnt proteins from mammalian cells. Lipoproteins may act as carriers for the intercellular movement and gradient formation of the lipid-linked morphogens Wingless and Hedgehog in Drosophila. To investigate whether such a mechanism can occur in mammals, we have studied Wnt release in cultured mammalian cells. Wnt3a associated with lipoproteins in the culture medium and not with extracellular vesicles or exosomes. Although Wnt3a was associated with both high-density lipoproteins (HDL) and low-density lipoproteins, only HDL allowed Wnt3a release from mouse fibroblasts. Remarkably, Wnt3a lacking its palmitate moiety was released in a lipoprotein-independent manner, demonstrating the dual role of palmitoylation in membrane and lipoprotein binding. We additionally found that Wnt3a can be released from enterocyte cell lines on endogenously expressed lipoproteins. We further discuss the physiological implications of our findings.