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E Maury1, N C Guérineau, C Comminges
1Institut Fédératif de Recherche en Immunologie Cellulaire et Moléculaire, Université Paul Sabatier and INSERM Unité 326, Phospholipides Membranaires, Signalisation Cellulaire et Lipoprotéines, Hôpital Purpan, Toulouse, Fran.
FEBS Letters
|February 22, 2000
Summary
A novel signaling pathway activates phospholipase C (PLC) to generate alkyl-TG, a lipid second messenger. This messenger regulates L-type Ca2+ channels, suggesting a new feedback mechanism in cellular signaling.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Pharmacology
Background:
- Endothelin-1 and platelet-derived growth factor induce rapid hydrolysis of 1-O-alkyl-2-acyl-sn-glycero-3-phosphoethanolamine (alkyl-PE) in aortic smooth muscle cells.
- This alkyl-PE is converted to 1-O-alkyl-2,3-diacyl-sn-glycerol (alkyl-TG), a process previously reported within seconds to minutes.
Purpose of the Study:
- To elucidate the signaling pathway responsible for alkyl-PE hydrolysis.
- To identify the role of alkyl-TG in cellular signaling and its interaction with calcium channels.
Main Methods:
- Investigated the role of phospholipase C (PLC) and pertussis toxin-sensitive G-proteins in alkyl-PE hydrolysis.
- Examined the involvement of L-type Ca2+ channels using activators (S(-)-BayK 8644) and inhibitors (nimodipine).
- Assessed the effect of alkyl-TG and diacylglycerol (DG) on L-type Ca2+ channel activity.
Main Results:
- Alkyl-PE hydrolysis is triggered by transient activation of a specific PLC regulated by pertussis toxin-sensitive G-proteins.
- This PLC activation is mediated by Ca2+ influx dependent on L-type Ca2+ channel activity.
- Low concentrations of alkyl-TG inhibit L-type Ca2+ channel opening, while DG has no effect.
Conclusions:
- A novel signaling pathway generates alkyl-TG as a lipid second messenger.
- Alkyl-TG acts as a negative feedback regulator of L-type Ca2+ channels.
- This pathway represents a previously unrecognized mechanism in cellular signaling and calcium regulation.