The Phosphatidylinositol 4-Kinases: Don’t Call it a Comeback
Phosphatidylinositol 4-phosphate (PtdIns4P) is a quantitatively minor membrane phospholipid which is the precursor of PtdIns(4,5)P 2 in the classical agonist-regulated phospholipase C signalling pathway. However, PtdIns4P also governs the recruitment and function of numerous trafficking molecules, principally in the Golgi complex. The majority of phosphoinositides (PIs) phosphorylated at the D4 position of the inositol headgroup are derived from PtdIns4P and play roles in a diverse array of fundamental cellular processes including secretion, cell migration, apoptosis and mitogenesis; therefore, PtdIns4P biosynthesis can be regarded as key point of regulation in many PI-dependent processes.
Two structurally distinct sequence families, the type II and type III PtdIns 4-kinases, are responsible for PtdIns4P synthesis in eukaryotic organisms. These important proteins are differentially expressed, localised and regulated by distinct mechanisms, indicating that the enzymes perform non-redundant roles in trafficking and signalling. In recent years, major advances have been made in our understanding of PtdIns4K biology and here we summarise current knowledge of PtdIns4K structure, function and regulation.
KeywordsGolgi complex Membrane traffic Phosphatidylinositol 4-phosphate Signalling
We are grateful to Prof. Justin Hsuan, Dr. Emma Clayton and Dr. Emily Chu for comments on the manuscript. SM and MGW acknowledge the support of the BBSRC (award BB/G021163/1).
- Balla A, Tuymetova G, Tsiomenko A, Varnai P, Balla T (2005) A plasma membrane pool of phosphatidylinositol 4-phosphate is generated by phosphatidylinositol 4-kinase type-III alpha: studies with the PH domains of the oxysterol binding protein and FAPP1. Mol Biol Cell 16:1282–1295PubMedCrossRefGoogle Scholar
- D’angelo G, Polishchuk E, Di Tullio G, Santoro M, Di Campli A, Godi A, West G, Bielawski J, Chuang CC, Van Der Spoel AC, Platt FM, Hannun YA, Polishchuk R, Mattjus P, de Matteis MA (2007) Glycosphingolipid synthesis requires FAPP2 transfer of glucosylceramide. Nature 449:62–67PubMedCrossRefGoogle Scholar
- De Graaf P, Zwart WT, van Dijken RA, Deneka M, Schulz TK, Geijsen N, Coffer PJ, Gadella BM, Verkleij AJ, Van Der Sluijs P, van Bergen En Henegouwen PM (2004) Phosphatidylinositol 4-kinasebeta is critical for functional association of rab11 with the Golgi complex. Mol Biol Cell 15:2038–2047PubMedCrossRefGoogle Scholar
- De Matteis MA, Di Campli A, D’angelo G (2007) Lipid-transfer proteins in membrane trafficking at the Golgi complex. Biochim Biophys Acta 1771:761–768Google Scholar
- Gromada J, Bark C, Smidt K, Efanov AM, Janson J, Mandic SA, Webb DL, Zhang W, Meister B, Jeromin A, Berggren PO (2005) Neuronal calcium sensor-1 potentiates glucose-dependent exocytosis in pancreatic beta cells through activation of phosphatidylinositol 4-kinase beta. Proc Natl Acad Sci USA 102:10303–10308PubMedCrossRefGoogle Scholar
- Kapp-Barnea Y, Ninio-Many L, Hirschberg K, Fukuda M, Jeromin A, Sagi-Eisenberg R (2006) Neuronal calcium sensor-1 and phosphatidylinositol 4-kinase beta stimulate extracellular signal-regulated kinase 1/2 signaling by accelerating recycling through the endocytic recycling compartment. Mol Biol Cell 17:4130–4141PubMedCrossRefGoogle Scholar
- Simons JP, Al-Shawi R, Minogue S, Waugh MG, Wiedemann C, Evangelou S, Loesch A, Sihra TS, King R, Warner TT, Hsuan JJ (2009) Loss of phosphatidylinositol 4-kinase 2alpha activity causes late onset degeneration of spinal cord axons. Proc Natl Acad Sci U S A 106:11535–11539PubMedCrossRefGoogle Scholar
- Wei YJ, Sun HQ, Yamamoto M, Wlodarski P, Kunii K, Martinez M, Barylko B, Albanesi JP, Yin HL (2002) Type II phosphatidylinositol 4-kinase beta is a cytosolic and peripheral membrane protein that is recruited to the plasma membrane and activated by Rac-GTP. J Biol Chem 277:46586–46593PubMedCrossRefGoogle Scholar
- Whitman M, Kaplan D, Roberts T, Cantley L (1987) Evidence for two distinct phosphatidylinositol kinases in fibroblasts. Implications for cellular regulation. Biochem J 247:165–174Google Scholar
- Yavari A, Nagaraj R, Owusu-Ansah E, Folick A, Ngo K, Hillman T, Call G, Rohatgi R, Scott MP, Banerjee U (2010) Role of lipid metabolism in smoothened depression in hedgehog signaling. Dev Cell 19:54–65Google Scholar