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Article

RAB10 Interacts with ABCB4 and Regulates Its Intracellular Traffic

by
Amel Ben Saad
1,2,
Virginie Vauthier
2,3,
Martine Lapalus
1,
Elodie Mareux
1,
Evangéline Bennana
4,
Anne-Marie Durand-Schneider
2,
Alix Bruneau
2,5,
Jean-Louis Delaunay
2,
Emmanuel Gonzales
1,6,
Chantal Housset
2,7,
Tounsia Aït-Slimane
2,
François Guillonneau
4,
Emmanuel Jacquemin
1,6 and
Thomas Falguières
1,*
1
Inserm, Université Paris-Saclay, Physiopathogénèse et traitement des maladies du foie, UMR_S 1193, Hepatinov, 91400 Orsay, France
2
Inserm, Sorbonne Université, Centre de Recherche Saint-Antoine (CRSA), UMR_S 938, Institute of Cardiometabolism and Nutrition (ICAN), 75012 Paris, France
3
Université de Paris, Institut Cochin, Inserm U1016, CNRS UMR 8104, 75014 Paris, France
4
3P5-Proteom’IC platform, Université de Paris, Institut Cochin, Inserm U1016, CNRS UMR8104, 75014 Paris, France
5
Department of Hepatology & Gastroenterology, Charité Universitätsmedizin Berlin, 13353 Berlin, Germany
6
Assistance Publique—Hôpitaux de Paris, Paediatric Hepatology & Paediatric Liver Transplant Department, Reference Center for Rare Paediatric Liver Diseases, FILFOIE, ERN Rare-Liver, Faculté de Médecine Paris-Saclay, CHU Bicêtre, 94270 Le Kremlin-Bicêtre, France
7
Assistance Publique—Hôpitaux de Paris, Hôpital Saint-Antoine, Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis, FILFOIE, ERN Rare-Liver, 75012 Paris, France
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(13), 7087; https://doi.org/10.3390/ijms22137087
Submission received: 27 May 2021 / Revised: 28 June 2021 / Accepted: 29 June 2021 / Published: 30 June 2021
(This article belongs to the Special Issue ABC Transporters in Human Diseases)
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Abstract

ABCB4 (ATP-binding cassette subfamily B member 4) is an ABC transporter expressed at the canalicular membrane of hepatocytes where it ensures phosphatidylcholine secretion into bile. Genetic variations of ABCB4 are associated with several rare cholestatic diseases. The available treatments are not efficient for a significant proportion of patients with ABCB4-related diseases and liver transplantation is often required. The development of novel therapies requires a deep understanding of the molecular mechanisms regulating ABCB4 expression, intracellular traffic, and function. Using an immunoprecipitation approach combined with mass spectrometry analyses, we have identified the small GTPase RAB10 as a novel molecular partner of ABCB4. Our results indicate that the overexpression of wild type RAB10 or its dominant-active mutant significantly increases the amount of ABCB4 at the plasma membrane expression and its phosphatidylcholine floppase function. Contrariwise, RAB10 silencing induces the intracellular retention of ABCB4 and then indirectly diminishes its secretory function. Taken together, our findings suggest that RAB10 regulates the plasma membrane targeting of ABCB4 and consequently its capacity to mediate phosphatidylcholine secretion.
Keywords: bile secretion; intracellular traffic; MDR3; phosphatidylcholine; RAB GTPase bile secretion; intracellular traffic; MDR3; phosphatidylcholine; RAB GTPase

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MDPI and ACS Style

Ben Saad, A.; Vauthier, V.; Lapalus, M.; Mareux, E.; Bennana, E.; Durand-Schneider, A.-M.; Bruneau, A.; Delaunay, J.-L.; Gonzales, E.; Housset, C.; et al. RAB10 Interacts with ABCB4 and Regulates Its Intracellular Traffic. Int. J. Mol. Sci. 2021, 22, 7087. https://doi.org/10.3390/ijms22137087

AMA Style

Ben Saad A, Vauthier V, Lapalus M, Mareux E, Bennana E, Durand-Schneider A-M, Bruneau A, Delaunay J-L, Gonzales E, Housset C, et al. RAB10 Interacts with ABCB4 and Regulates Its Intracellular Traffic. International Journal of Molecular Sciences. 2021; 22(13):7087. https://doi.org/10.3390/ijms22137087

Chicago/Turabian Style

Ben Saad, Amel, Virginie Vauthier, Martine Lapalus, Elodie Mareux, Evangéline Bennana, Anne-Marie Durand-Schneider, Alix Bruneau, Jean-Louis Delaunay, Emmanuel Gonzales, Chantal Housset, and et al. 2021. "RAB10 Interacts with ABCB4 and Regulates Its Intracellular Traffic" International Journal of Molecular Sciences 22, no. 13: 7087. https://doi.org/10.3390/ijms22137087

APA Style

Ben Saad, A., Vauthier, V., Lapalus, M., Mareux, E., Bennana, E., Durand-Schneider, A.-M., Bruneau, A., Delaunay, J.-L., Gonzales, E., Housset, C., Aït-Slimane, T., Guillonneau, F., Jacquemin, E., & Falguières, T. (2021). RAB10 Interacts with ABCB4 and Regulates Its Intracellular Traffic. International Journal of Molecular Sciences, 22(13), 7087. https://doi.org/10.3390/ijms22137087

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