Research ArticleDevelopmental Biology

Temporal and spatial regulation of epsin abundance and VEGFR3 signaling are required for lymphatic valve formation and function

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Science Signaling  14 Oct 2014:
Vol. 7, Issue 347, pp. ra97
DOI: 10.1126/scisignal.2005413

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Ensuring a One-Way Flow of Lymph

Lymphatic vessels return lymph, which consists of fluid and mostly immune cells that go into the tissues from the blood, back to the circulation. Valves in lymphatic vessels ensure that lymph flows in one direction into veins and prevent the accumulation of lymph in tissues, a condition called edema. The receptor VEGFR3 is required for lymphatic vessel development. Liu et al. noted that the regions of developing lymphatic vessels that became valves had high VEGFR3 amounts but low amounts of epsin 1 and 2, proteins that are involved in endocytosis. They determined that epsin 1 and 2 suppressed VEGFR3 signaling in collecting lymphatic trunks by triggering endocytosis and degradation of VEGFR3. Furthermore, mice lacking epsin 1 and 2 in the endothelial cells that line lymphatic vessels had defective lymphatic valves and impaired drainage. Lymphatic valve formation was restored in these mice by deletion of a single allele of Vegfr3 or treatment with a VEGFR3 inhibitor.

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