Wunen, a Drosophila lipid phosphate phosphatase, is required for septate junction-mediated barrier function

Abstract

SUMMARYLipid phosphate phosphatases (LPPs) are integral membrane enzymes that regulate the levels of bioactive lipids such as sphingosine 1-phosphate and lysophosphatidic acid. The Drosophila LPPs Wunen (Wun) and Wunen-2 (Wun2) have a well-established role in regulating the survival and migration of germ cells. We now show that wun has an essential tissue-autonomous role in development of the trachea: the catalytic activity of Wun is required to maintain septate junction (SJ) paracellular barrier function, loss of which causes failure to accumulate crucial luminal components, suggesting a role for phospholipids in SJ function. We find that the integrity of the blood-brain barrier is also lost in wun mutants, indicating that loss of SJ function is not restricted to the tracheal system. Furthermore, by comparing the rescue ability of different LPP homologs we show that wun function in the trachea is distinct from its role in germ cell migration.

Lipid phosphate phosphatases and their roles in mammalian physiology and pathology

“…Furthermore, mutation of Wunens in Drosophila causes impaired migration of primordial germ cells. The death of germ cells can be rescued by expression of human and mouse LPP3, but not human LPP1 or mouse LPP2 ( 102,103 ).…”

“…Wunen and Wunen-2 show similar catalytic activity against LPA relative to mammalian LPPs ( 102 ). They are required by Drosophila in controlling primordial germ cell migration and maintaining the septate junction paracellular barrier during development of the trachea (102)(103)(104). Unlike vertebrate cells, insect cells do not express LPA and S1P receptors.…”

Lipid phosphate phosphatase-1 expression in cancer cells attenuates tumor growth and metastasis in mice

“…Work with the Drosphila LPPs, Wunen and Wunen-2, confi rms a role in controlling the survival and migration of germ cells. In addition, the Wunen proteins serve an essential tissue-autonomous role in development of the trachea and in the integrity of the blood-brain barrier ( 22 ).…”

Lipid metabolism in <italic>Drosophila</italic>: development and disease

“…Besides the wellestablished role in germ cell migration, wun was found to regulate the function of septate junction. In wun mutants, the integrity of septate junction in the trachea and the blood-brain barrier is lost, indicating a role for phospholipids in septate junction function [45]. Together, sphingolipid and phospholipid metabolisms are critical for normal development and the subsequent integrity of adult tissues.…”