Vitamin C transport in neurons and epithelia is regulated by secretory carrier-associated membrane protein-2 (SCAMP2).

Autor: Rashid MA; Department of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, WI 53226, United States., Lin-Moshier Y; Department of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, WI 53226, United States., Gunaratne GS; Department of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, WI 53226, United States., Subramanian S; Department of Medicine, University of California, Irvine, CA 92697, United States., Marchant JS; Department of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, WI 53226, United States., Subramanian VS; Department of Medicine, University of California, Irvine, CA 92697, United States. Electronic address: vsubrama@uci.edu.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2023 Mar 01; Vol. 230, pp. 123205. Date of Electronic Publication: 2023 Jan 09.
DOI: 10.1016/j.ijbiomac.2023.123205
Abstrakt: The human sodium-dependent vitamin C transporter-1 (hSVCT1) is localized at the apical membrane domain of polarized intestinal and renal epithelial cells to mediate ascorbic acid (AA) uptake. Currently, little is known about the array of interacting proteins that aid hSVCT1 trafficking and functional expression at the cell surface. Here we used an affinity tagging ('One-STrEP') and proteomic approach to identify hSVCT1 interacting proteins, which resolved secretory carrier-associated membrane protein-2 (SCAMP2) as a novel accessary protein partner. SCAMP2 was validated as an accessory protein by co-immunoprecipitation with hSVCT1. Co-expression of hSVCT1 and SCAMP2 in HEK-293 cells revealed both proteins co-localized in intracellular structures and at the plasma membrane. Functionally, over-expression of SCAMP2 potentiated 14 C-AA uptake, and reciprocally silencing endogenous SCAMP2 decreased 14 C-AA uptake. Finally, knockdown of endogenous hSVCT1 or SCAMP2 impaired differentiation of human-induced pluripotent stem cells (hiPSCs) toward a neuronal fate. These results establish SCAMP2 as a novel hSVCT1 accessary protein partner that regulates AA uptake in absorptive epithelia and during neurogenesis.
Competing Interests: Declaration of competing interest No potential conflict of interest was reported by the author(s).
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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