Mammalian Wnt3a is released on lipoprotein particles

Area of Science:

• Cell biology
• Molecular biology
• Biochemistry

Background:

• Wnt proteins are crucial lipid-linked morphogens involved in cell signaling.
• Their release and intercellular transport mechanisms in mammals remain largely unknown.
• Lipoproteins are implicated in the transport of morphogens in Drosophila.

Purpose of the Study:

• To investigate the role of lipoproteins in the release and intercellular transport of Wnt proteins from mammalian cells.
• To determine if Wnt proteins associate with lipoproteins for extracellular movement.
• To elucidate the mechanism of Wnt release, focusing on Wnt3a.

Main Methods:

• Cultured mammalian cells (fibroblasts and enterocytes) were used.
• Wnt3a association with lipoproteins, extracellular vesicles, and exosomes was analyzed.
• The effect of high-density lipoproteins (HDL) and low-density lipoproteins (LDL) on Wnt3a release was assessed.
• Wnt3a variants lacking palmitate were studied to understand palmitoylation's role.

Main Results:

• Wnt3a associated with lipoproteins in the culture medium, not extracellular vesicles.
• HDL, but not LDL, facilitated Wnt3a release from mouse fibroblasts.
• Wnt3a lacking its palmitate moiety showed lipoprotein-independent release.
• Wnt3a release was observed from enterocyte cell lines expressing endogenous lipoproteins.

Conclusions:

• Lipoproteins, especially HDL, play a significant role in the release of Wnt3a from mammalian cells.
• Palmitoylation is critical for both Wnt3a membrane association and lipoprotein binding.
• This study reveals a novel lipoprotein-mediated mechanism for Wnt protein transport in mammals.