Abstract
In neurons, the plasma membrane is functionally separated into several distinct segments. Neurons form these domains by delivering selected components to and by confining them within each segment of the membrane. Although some mechanisms of the delivery are elucidated, that of the confinement is unclear. We show here that 1-oleoyl-2-palmitoyl-phosphatidylcholine (OPPC), a unique molecular species of phospholipids, is concentrated at the protrusion tips of several neuronal culture cells and the presynaptic area of neuronal synapses of the mouse brain. In PC12 cells, NGF-stimulated neuronal differentiation induces a phospholipase A1 activity at the protrusion tips, which co-localizes with the OPPC domain. Inhibition of the phospholipase A1 activity leads to suppression of phospholipid remodeling in the tip membrane and results in disappearance of the OPPC at the tips. In these cells, confinement of dopamine transporter and Gαo proteins to the tip was also disrupted. These findings link the lateral distribution of the molecular species of phospholipids to the formation of functional segments in the plasma membrane of neurons and to the mechanism of protein confinement at the synapse.
Highlights
In neurons, the plasma membrane is separated into functional segments
The antigen of monoclonal antibody #15 (mAb#15) was extracted from the cells with cold methanol (Fig. 1G), and the antigen in the methanol extract was resistant to a protease K digestion, indicating the lipid nature of the antigen
OPPC Domain at the Neuronal Synapse—To examine whether the formation of the OPPC domain at protrusion tips is a peculiarity of PC12 cells, we investigated several other cell types. mAb#15 antigen was localized at the tips of processes in Neuro-2a cells but not in COS-7 cells (Fig. 4A)
Summary
The plasma membrane is separated into functional segments. Results: A phospholipid with a unique acyl chain composition is concentrated at the tips of neuronal projections, which is necessary for the confinement of proteins at the site. Confinement of dopamine transporter and G␣o proteins to the tip was disrupted These findings link the lateral distribution of the molecular species of phospholipids to the formation of functional segments in the plasma membrane of neurons and to the mechanism of protein confinement at the synapse. The plasma membrane is functionally separated into the somatodendritic membrane and several distinct segments of the axon These membrane compartments are essential for the directional propagation of action potential from the soma to the axon tip and for formation of neural circuits among neurons; the mechanisms underlining this compartmentalization are unclear. We describe our findings linking the remodeling process of phospholipids to the functional compartmentalization of the presynaptic area in the neuronal plasma membrane
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