The neurosecretory vesicle protein phogrin functions as a phosphatidylinositol phosphatase to regulate insulin secretion.

The Journal of Biological Chemistry
Leslie A CaromileDaniel F Bowen-Pope

Abstract

Phogrin is a transmembrane protein expressed in cells with stimulus-coupled peptide hormone secretion, including pancreatic beta cells, in which it is localized to the membrane of insulin-containing dense-core vesicles. By sequence, phogrin is a member of the family of receptor-like protein-tyrosine phosphatases, but it contains substitutions in conserved catalytic sequences, and no significant enzymatic activity for phogrin has ever been reported. We report here that phogrin is able to dephosphorylate specific inositol phospholipids, including phosphatidylinositol (PI) 3-phosphate and PI 4,5-diphosphate but not PI 3,4,5-trisphosphate. The phosphatidylinositol phosphatase (PIPase) activity of phogrin was measurable but low when evaluated by the ability of a catalytic domain fusion protein to hydrolyze soluble short-chain phosphatidylinositol phospholipids. Unlike most PIPases, which are cytoplasmic proteins that associate with membranes, mature phogrin is a transmembrane protein. When the transmembrane form of phogrin was overexpressed in mammalian cells, it reduced plasma membrane phosphatidylinositol 4,5-disphosphate levels in a dose-dependent manner. When purified and assayed in vitro, the transmembrane form had a specific a...Continue Reading

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Citations

Aug 1, 2013·Human Molecular Genetics·Rafael PulidoWiljan J A J Hendriks
May 28, 2013·Biochimica Et Biophysica Acta·Wiljan J A J Hendriks, Rafael Pulido
Oct 30, 2014·Frontiers in Endocrinology·Chris Li, Kyuhyung Kim
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Aug 28, 2021·Clinical and Experimental Pharmacology & Physiology·Chunting LuQiping Shi

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