Our FABulous VACation: a decade of phosphatidylinositol 3,5-bisphosphate.
PtdIns(3,5)P2 was discovered about a decade ago and much of the machinery that makes, degrades and senses it has been uncovered. Despite this, we still lack a complete understanding of how the pieces fit together but some patterns are beginning to emerge. Molecular functions for PtdIns(3,5)P2 are also elusive, but the identification of effectors offers a way into some of these processes. An examination of the defects associated with loss of synthesis of PtdIns(3,5)P2 in lower and higher eukaryotes begins to suggest a unifying theme; this lipid regulates membrane retrieval via retrograde trafficking from distal compartments to organelles that are more proximal in the endocytic/lysosomal system. Another unifying theme is stress signalling to organelles, possibly both to change their morphology in response to external insults and to maintain the lumenal pH or membrane potential of organelles. The next few years seem likely to uncover details of the molecular mechanisms underlying the biology of this fascinating lipid. This review also highlights some areas where further research is needed.
Dove
Stephen K
SK
School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK. s.k.dove@bham.ac.uk
Johnson
Zoë E
ZE
D000818:Animals; D004330:Drosophila / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018129:Phosphatidylinositol Phosphates; D029701:Saccharomyces cerevisiae Proteins; C452435:VAC14 protein, S cerevisiae; C494631:VAC14 protein, human; C452436:VAC7 protein, S cerevisiae; C106336:phosphatidylinositol 3,5-diphosphate; C095504:FAB1 protein, S cerevisiae; C514108:Fab1 protein, Drosophila; D017853:Phosphotransferases (Alcohol Group Acceptor)