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PMID: 12646710 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Phosphatidylinositol 4-kinase type IIalpha is responsible for the phosphatidylinositol 4-kinase activity associated with synaptic vesicles.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 100 ·No. 7 ·2003-04-01 ·Pages 3995-4000

Guo J, Wenk MR, Pellegrini L, Onofri F, Benfenati F, De Camilli P

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.

MeSH Terms
1-Phosphatidylinositol 4-Kinase/metabolism Animals Biomarkers/analysis Brain/enzymology,physiology Cloning, Molecular Isoenzymes/metabolism Microscopy, Immunoelectron Minor Histocompatibility Antigens Models, Neurological Nerve Tissue Proteins/analysis Organelles/enzymology Phosphatidylinositols/metabolism Phosphotransferases (Alcohol Group Acceptor)/metabolism Rats Recombinant Fusion Proteins/metabolism Recombinant Proteins/metabolism Subcellular Fractions/enzymology Synaptic Vesicles/enzymology
Chemicals
Biomarkers Isoenzymes Minor Histocompatibility Antigens Nerve Tissue Proteins Phosphatidylinositols Recombinant Fusion Proteins Recombinant Proteins Phosphotransferases (Alcohol Group Acceptor) 1-Phosphatidylinositol 4-Kinase phosphatidylinositol phosphate 4-kinase
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Guo Jun
Howard Hughes Medical Institute and Department of Cell Biology, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06510, USA.
Wenk Markus R
Pellegrini Lorenzo
Onofri Franco
Benfenati Fabio
De Camilli Pietro
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44 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0230488100
Published
2003-04-01
Epub
2003-00-19
Pages
3995-4000
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC153036
Subset
IM
Grants
NIDDK NIH HHS · DK54913 · United States
Telethon · 1131 · Italy
NINDS NIH HHS · R01 NS036251 · United States
NINDS NIH HHS · NS36251 · United States
NINDS NIH HHS · R37 NS036251 · United States
External Links
PubMed source DOI: 10.1073/pnas.0230488100 PMC Full Text View journal details
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