Unexpected player in regulation of blood cholesterol levels

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Unexpected player in regulation of blood cholesterol levels

Kinesins are motor proteins that "walk" along microtubules and transport various cargoes throughout the cell. A study in The Journal of Cell Biology uncovers an unexpected role for one kinesin in the pathway that regulates cholesterol levels in the blood.

Researchers from The University of Tokyo in Japan studied mice lacking KIF13B, one of 45 kinesins in the human genome. KIF13B is particularly abundant in the liver, and KIF13B mutant mice were found to have elevated levels of cholesterol in their blood.

The researchers discovered that KIF13B concentrates within liver cells at the spot where material such as LDL—the "bad" form of cholesterol—is taken up from the bloodstream. LDL enters the cell through endocytosis, a process in which cells absorb molecules by engulfing them. Endocytosis can be mediated in the cell membrane by small clathrin-coated vesicles or by small pits called caveolae. The cell membrane receptor LRP1 binds and engulfs LDL through both of these pathways.

The researchers discovered that LRP1 and KIF13B appeared together at the cell membrane and that KIF13B promoted the endocytosis of LRP1 by recruiting the receptor, along with LDL, into caveolae.

"Clathrin-mediated endocytosis has been studied intensively," says senior author Nobutaka Hirokawa. "But this is the first study to identify a mechanism for caveolin-mediated internalization."

Surprisingly, KIF13B's motor functions were not employed in this process. Rather, the kinesin was found to work as a scaffold at the cell membrane to help link LRP1 to caveolae.

"This scaffolding function is very unexpected for a motor protein," says Hirokawa. "But, after LRP1 is internalized, KIF13B could work as a motor to transport endosomes through the cytoplasm."



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The authors now want to investigate whether KIF13B also controls LRP1 endocytosis and blood cholesterol levels in humans. And, based on its role in the liver, they suspect that KIF13B could similarly control endocytosis of cell surface proteins in other organs as well.

Kanai, Y., et al. 2014. J. Cell Biol. doi:10.1083/jcb.201309066.

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