Chromogranin A regulates the dynamics of neurosecretion through its interaction with phosphatidic acid

Abstract Altered neurosecretion is a common feature of diverse pathophysiological conditions, including central nervous system disorders, hypertension, and tumorigenesis, where chromogranin A (CgA) is widely used as a biomarker, and both phosphatidic acid (PA) synthesis and catecholamine (CA) secretion are dysregulated. Here, we identify a direct interaction between CgA and PA at the plasma membrane of living cells using a newly developed synthetic PA fluorescent probe and Förster’s resonance energy transfer (FRET) combined with fluorescence lifetime imaging microscopy (FLIM). Confocal microscopy and transmission electron microscopy (TEM) further reveal that this interaction is spatially confined to exocytic sites. Using Total Internal Reflection Fluorescence microscopy (TIRF-M), we show that expression of a CgA variant lacking the PA-binding domain (PABD) in COS-7 cells increases the frequency of exocytic events and accelerates CgA release kinetics. In chromaffin cells, amperometry and live tracking of exocytosis-endocytosis demonstrate that CgA overexpression enhances granular CA content, extends fusion pore opening, and accelerates exocytosis-endocytosis coupling, effects that are abolished upon expression of CgA variant. Together, these findings unveil a new role of CgA/PA interaction in fine-tuning neurohormone secretion, suggesting unexplored avenues for restoring neurosecretion in disease-relevant contexts.

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Publication Details

Journal
bioRxiv (Cold Spring Harbor Laboratory)
Published
2026-02-02
DOI
https://doi.org/10.64898/2026.01.29.699889
Primary Topic
Cellular transport and secretion
Type
article
Field-Weighted Citation Impact
0.00

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article

Chromogranin A regulates the dynamics of neurosecretion through its interaction with phosphatidic acid

Thomas Ferrand, Fanny Laguerre, Maite Gilabert Montero, N. Chartrel et al.
bioRxiv (Cold Spring Harbor Laboratory)
Cellular transport and secretion
article

Chromogranin A regulates the dynamics of neurosecretion through its interaction with phosphatidic acid

Thomas Ferrand, Fanny Laguerre, Maite Gilabert Montero, N. Chartrel, Sylvette Chasserot‐Golaz, Lydie Jeandel, Luca Grumolato, Cathy Royer, Dorthe Cartier, Ludovic Galas, Damien Schapman, Lina Riachy, Ji‐Young Lee, Sophie Bernard, Nicolás Marcelo Vitale, Alexander Wolf, Y. Anouar, Antoine Schlichter, Brice Beauvais, Caroline Bérard, Sebastien BALIEU, Pierre-Yves RENARD
article en

Abstract

Abstract Altered neurosecretion is a common feature of diverse pathophysiological conditions, including central nervous system disorders, hypertension, and tumorigenesis, where chromogranin A (CgA) is widely used as a biomarker, and both phosphatidic acid (PA) synthesis and catecholamine (CA) secretion are dysregulated. Here, we identify a direct interaction between CgA and PA at the plasma membrane of living cells using a newly developed synthetic PA fluorescent probe and Förster’s resonance energy transfer (FRET) combined with fluorescence lifetime imaging microscopy (FLIM). Confocal microscopy and transmission electron microscopy (TEM) further reveal that this interaction is spatially confined to exocytic sites. Using Total Internal Reflection Fluorescence microscopy (TIRF-M), we show that expression of a CgA variant lacking the PA-binding domain (PABD) in COS-7 cells increases the frequency of exocytic events and accelerates CgA release kinetics. In chromaffin cells, amperometry and live tracking of exocytosis-endocytosis demonstrate that CgA overexpression enhances granular CA content, extends fusion pore opening, and accelerates exocytosis-endocytosis coupling, effects that are abolished upon expression of CgA variant. Together, these findings unveil a new role of CgA/PA interaction in fine-tuning neurohormone secretion, suggesting unexplored avenues for restoring neurosecretion in disease-relevant contexts.

bioRxiv (Cold Spring Harbor Laboratory)
Centre National de la Recherche Scientifique (FR), Inserm (FR), Normandie Université (FR), Institut des Neurosciences Cellulaires et Intégratives (FR), Institute for Research and Innovation in Biomedicine (FR), Université de Rouen Normandie (FR), Université de Strasbourg (FR), Institut National des Sciences Appliquées Rouen Normandie (FR)
Infrastructures en Biologie Santé et Agronomie, European Commission, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Fondation pour la Recherche Médicale, Centre National de la Recherche Scientifique, Région Normandie, European Regional Development Fund
Affordable and clean energy
Openalex Percentile: Top 71%
Cellular transport and secretion
DOIOpen Access PDFOpenAlex
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