title: Phosphatidylinositol 4-kinase type IIalpha is responsible for the phosphatidylinositol 4-kinase activity associated with synaptic vesicles.
abstract: Phosphorylation of inositol phospholipids plays a key role in cellular regulation via the generation of intracellular second messengers. In addition, it represents a mechanism to regulate interactions of the lipid bilayer with proteins and protein scaffolds involved in vesicle budding, cytoskeletal organization, and signaling. Generation of phosphatidylinositol 4-phosphate [PI(4)P] from phosphatidylinositol (PI) is an important step in this metabolic pathway because PI(4)P is a precursor of other important phosphoinositides and has protein binding properties of its own. We report here that a PI 4-kinase (PI4K) activity previously reported on synaptic vesicles is accounted for by the alpha isoform of the recently characterized type II PI4K (PI4KII) family. PI4KIIalpha, which also accounts for the bulk of PI4K activity in brain extracts, is concentrated at synapses and in the region of the Golgi complex in neuronal perikarya. Our results provide new evidence for the occurrence of a cycle of phosphoinositide synthesis and hydrolysis nested within the exo-endocytic cycle of synaptic vesicles and point to PI4KIIalpha as a critical player in this cycle.
authors.affiliation: Howard Hughes Medical Institute and Department of Cell Biology, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06510, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
authors.forename: Markus R
authors.initials: MR
authors.lastname: Wenk
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Pellegrini
authors.forename: Franco
authors.initials: F
authors.lastname: Onofri
authors.forename: Fabio
authors.initials: F
authors.lastname: Benfenati
authors.forename: Pietro
authors.initials: P
authors.lastname: De Camilli
mesh_terms: D019870:1-Phosphatidylinositol 4-Kinase / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000201:enzymology / Q000502:physiology; D003001:Cloning, Molecular; D007527:Isoenzymes / Q000378:metabolism*; D016253:Microscopy, Immunoelectron; D015778:Minor Histocompatibility Antigens; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000032:analysis; D015388:Organelles / Q000201:enzymology; D010716:Phosphatidylinositols / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013347:Subcellular Fractions / Q000201:enzymology; D013572:Synaptic Vesicles / Q000201:enzymology*
chemical_list: D015415:Biomarkers; D007527:Isoenzymes; D015778:Minor Histocompatibility Antigens; D009419:Nerve Tissue Proteins; D010716:Phosphatidylinositols; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); D019870:1-Phosphatidylinositol 4-Kinase; C402182:phosphatidylinositol phosphate 4-kinase