The Many Roles of Type II Phosphatidylinositol 4‐Kinases in Membrane Trafficking: New Tricks for Old Dogs

• Published in: BioEssays Vol. 40; no. 2
• Main Author: Minogue, Shane
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.02.2018
• Subjects: 1-Phosphatidylinositol 4-Kinase - physiology; Animals; Cancer; Cell Membrane - enzymology; endosome; Humans; Kinases; Lipids - biosynthesis; Membrane trafficking; Neoplasms - enzymology; Nervous System Diseases - enzymology; Phosphates; Phosphatidylinositol 4-phosphate; phosphatidylinositol 4‐kinase; Phosphatidylinositol Phosphates - metabolism; Protein Transport; Proteins; Signal Transduction; Signaling; sorting; TGN; endosome; TGN; membrane trafficking; sorting; phosphatidylinositol 4-kinase
• ISSN: 0265-9247; 1521-1878
• DOI: 10.1002/bies.201700145

The type II phosphatidylinositol 4‐kinases (PI4KIIs) produce the lipid phosphatidylinositol 4‐phosphate (PtdIns4P) and participate in a confusing variety of membrane trafficking and signaling roles. This review argues that both historical and contemporary evidence supports the function of the PI4KIIs in numerous trafficking pathways, and that the key to understanding the enzymatic regulation is through membrane interaction and the intrinsic membrane environment. By summarizing new research and examining the trafficking roles of the PI4KIIs in the context of recently solved molecular structures, I highlight how mechanisms of PI4KII function and regulation are providing insights into the development of cancer and in neurological disease. I present an integrated view connecting the cell biology, molecular regulation, and roles in whole animal systems of these increasingly important proteins. The type II phosphatidylinositol 4‐kinases (PI4KIIs) are versatile mediators of membrane trafficking, controlling pathways that impact on disease. Recent advances suggest that the membrane lipid environment regulates enzyme activity and that the complexity of trafficking routes can be explained by the ability of these kinases to promote membrane trafficking in different directions.