SNX19 Interacts with Caveolin-1 and Flotillin-1 to Regulate DR Endocytosis and Signaling

Authors

• Bibhas Amatya, Division of Kidney Diseases & Hypertension, Department of Medicine, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USA.
• Jacob Q. Polzin, Division of Kidney Diseases & Hypertension, Department of Medicine, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USA.
• Van A. Villar, Division of Kidney Diseases & Hypertension, Department of Medicine, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USA.
• Jiang Yang, Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, 20 Penn Street, HSF II, Baltimore, MD 21201, USA.
• Prasad Konkalmatt, Division of Kidney Diseases & Hypertension, Department of Medicine, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USA.
• Xiaoyan Wang, Division of Kidney Diseases & Hypertension, Department of Medicine, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USA.
• Raisha C. Cadme, Division of Kidney Diseases & Hypertension, Department of Medicine, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USA.
• Peng Xu, Department of Pathology, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA.
• John J. Gildea, Department of Pathology, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA.
• Santiago Cuevas, Division of Kidney Diseases & Hypertension, Department of Medicine, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USA.
• Ines Armando, Division of Kidney Diseases & Hypertension, Department of Medicine, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USA.
• Robin A. Felder, Department of Pathology, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA.
• Pedro A. Jose, Division of Kidney Diseases & Hypertension, Department of Medicine, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USA.
• Hewang Lee, Division of Kidney Diseases & Hypertension, Department of Medicine, The George Washington University School of Medicine & Health Sciences, Washington, DC 20052, USA.

Document Type

Journal Article

Publication Date

2-15-2025

Journal

Biomedicines

Volume

13

Issue

2

DOI

10.3390/biomedicines13020481

Keywords

SNX19; caveolin-1; dopamine D1 receptor; endocytosis; flotillin-1; lipid raft

Abstract

Sorting nexin 19 (SNX19) is important in the localization and trafficking of the dopamine D receptor (DR) to lipid raft microdomains. However, the interaction between SNX19 and the lipid raft components caveolin-1 or flotillin-1 and, in particular, their roles in the cellular endocytosis and cell membrane trafficking of the DR have not been determined. Caveolin-1 and flotillin-1 motifs were analyzed by in silico analysis; colocalization was observed by confocal immunofluorescence microscopy; protein-protein interaction was determined by co-immunoprecipitation. In silico analysis revealed the presence of putative caveolin-1 and flotillin-1 binding motifs within SNX19. In mouse and human renal proximal tubule cells (RPTCs), SNX19 was localized mainly in lipid rafts. In mouse RPTCs transfected with wild-type (WT) Snx19, fenoldopam (FEN), a D-like receptor agonist, increased the colocalization of SNX19 with caveolin-1 and flotillin-1. FEN also increased the co-immunoprecipitation of SNX19 with caveolin-1 and flotillin-1, effects that were prevented by SCH39166, a D-like receptor antagonist. The FEN-mediated increase in the residence of SNX19 in lipid rafts and the colocalization of the DR with caveolin-1 and flotilin-1 were attenuated by the deletion of a caveolin-1 (YHTVNRRYREF) (ΔCav1) or a flotillin-1 (EEGPGTETETGLPVS) (ΔFlot1) binding motif. The FEN-mediated increase in intracellular cAMP production was also impaired by the deletion of either the flotillin-1 or caveolin-1 binding motif. Nocodazole, a microtubule depolymerization inhibitor, interfered with the FEN-mediated increase in the colocalization between SNX19 and DR. SNX19 contains caveolin-1 and flotillin-1 binding motifs, which play an important role in DR endocytosis and signaling.

APA Citation

Amatya, Bibhas; Polzin, Jacob Q.; Villar, Van A.; Yang, Jiang; Konkalmatt, Prasad; Wang, Xiaoyan; Cadme, Raisha C.; Xu, Peng; Gildea, John J.; Cuevas, Santiago; Armando, Ines; Felder, Robin A.; Jose, Pedro A.; and Lee, Hewang, "SNX19 Interacts with Caveolin-1 and Flotillin-1 to Regulate DR Endocytosis and Signaling" (2025). GW Authored Works. Paper 6567.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/6567

Department

Medicine