Phosphatidic acid metabolism regulates neuroendocrine secretion but is not under the direct control of lipins.

Fiche publication

Date publication

janvier 2020

Journal

IUBMB life

Auteurs

Membres identifiés du Cancéropôle Est :
Dr BADER Marie-France , Dr GASMAN Stéphane , Dr CHASSEROT-GOLAZ Sylvette , Dr VITALE Nicolas

Tous les auteurs :
Baneux C, Tanguy E, Thahouly T, Vitale A, Chasserot-Golaz S, Bader MF, Gasman S, Vitale N

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/31967386

Résumé

Phosphatidic acid (PA) produced by phospholipase D1 has been shown to contribute to secretory vesicle exocytosis in a large number of cell models. Among various hypotheses, PA may contribute to recruit and/or activate at the exocytotic site a set of proteins from the molecular machinery dedicated to secretion, but also directly influence membrane curvature thereby favoring membrane rearrangements required for membrane fusion. The release of informative molecules by regulated exocytosis is a tightly controlled process. It is thus expected that PA produced to trigger membrane fusion should be rapidly metabolized and converted in a lipid that does not present similar characteristics. PA-phosphatases of the lipin family are possible candidates as they convert PA into diacylglycerol. We show here that lipin 1 and lipin 2 are expressed in neuroendocrine cells where they are cytosolic, but also partially associated with the endoplasmic reticulum. Silencing of lipin 1 or 2 did not affect significantly either basal or evoked secretion from PC12 cells, suggesting that it is unlikely that conversion of PA into a secondary lipid by lipins might represent a regulatory step in exocytosis in neurosecretory cells. However, in agreement with a model in which PA-metabolism could contribute to prevent entering into exocytosis of additional secretory vesicles, ectopic expression of lipin1B-GFP in bovine chromaffin cells reduced the number of exocytotic events as revealed by carbon fiber amperometry recording. Furthermore, individual spike parameters reflecting fusion pore dynamics were also modified by lipin1B-GFP, suggesting that a tight control of PA levels represents an important regulatory step of the number and kinetic of exocytotic events.