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Phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) is needed for retrograde membrane trafficking from lysosomal and late endosomal compartments and its synthesis is tightly regulated. But how cells regulate PtdIns(3,5)P2 synthesis--for example, in response to hyperosmotic shock--remains unexplained. A paper from the Weisman group gives the most complete picture so far of a multiprotein complex that controls PtdIns(3,5)P2 synthesis and explains how a VAC14 mutation functionally impairs the scaffold protein at the heart of the complex and causes a neurodegenerative condition in mice.
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Michell et al. (2009) studied this question.
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