Regulation of presynaptic phosphatidylinositol 4,5-biphosphate by neuronalactivity

Citation
Kd. Micheva et al., Regulation of presynaptic phosphatidylinositol 4,5-biphosphate by neuronalactivity, J CELL BIOL, 154(2), 2001, pp. 355-368
Citations number
59
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
JOURNAL OF CELL BIOLOGY
ISSN journal
0021-9525 → ACNP
Volume
154
Issue
2
Year of publication
2001
Pages
355 - 368
Database
ISI
SICI code
0021-9525(20010723)154:2<355:ROPP4B>2.0.ZU;2-B
Abstract
Phosphatidylinositol 4,5-biphosphate (PIP2) has been implicated in a variet y of cellular processes, including synaptic vesicle recycling. However, lit tle is known about the spatial distribution of this phospholipid in neurons and its dynamics. In this study, we have focused on these questions by tra nsiently expressing the phospholipase C (PLC)-delta1 pleckstrin homology (P H) domain fused to green fluorescent protein (GFP) in cultured hippocampal neurons. This PH domain binds specifically and with high affinity to PIP2. Live confocal imaging revealed that in resting cells, PH-GFP is localized p redominantly on the plasma membrane. Interestingly, no association of PH-GF P with synaptic vesicles in quiescent neurons was observed, indicating the absence of detectable PIP2 on mature synaptic vesicles. Electrical stimulat ion of hippocampal neurons resulted in a decrease of the PH-GFP signal at t he plasma membrane, most probably due to a PLC-mediated hydrolysis of PIP2. This was accompanied in the majority of presynaptic terminals by a marked increase in the cytoplasmic PH-GFP signal, localized most probably on fresh ly endocytosed membranes. Further investigation revealed that the increase in PH-GFP signal was dependent on the activation of N-methyl-D-aspartate re ceptors and the consequent production of nitric oxide (NO). Thus, PIP2 in t he presynaptic terminal appears to be regulated by postsynaptic activity vi a a retrograde action of NO.