Low-density lipoprotein (LDL) receptor-related protein-1 (LRP1) is expressed in retinal Müller glial cells (MGCs) and regulates intracellular translocation to the plasma membrane (PM) of the membrane proteins involved in cellular motility and activity. Different functions of MGCs may be influenced by insulin, including the removal of extracellular glutamate in the retina. In the present work, we investigated whether insulin promotes LRP1 translocation to the PM in the Müller glial-derived cell line MIO-M1 (human retinal Müller glial cell-derived cell line). We demonstrated that LRP1 is stored in small vesicles containing an approximate size of 100 nm (mean diameter range of 100–120 nm), which were positive for sortilin and VAMP2, and also incorporated GLUT4 when it was transiently transfected. Next, we observed that LRP1 translocation to the PM was promoted by insulin-regulated exocytosis through intracellular activation of the IR/PI3K/Akt axis and Rab-GTPase proteins such as Rab8A and Rab10. In addition, these Rab-GTPases regulated both the constitutive and insulin-induced LRP1 translocation to the PM. Finally, we found that dominant-negative Rab8A and Rab10 mutants impaired insulin-induced intracellular signaling of the IR/PI3K/Akt axis, suggesting that these GTPase proteins as well as the LRP1 level at the cell surface are involved in insulin-induced IR activation.
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May 2018
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A depiction of Clostridium spp. In this issue of the Biochemical Journal, St. John et al. examine the mechanisms of a novel GH30-8 endoxylanase in solventogenic Clostridium; for details see pages 1533–1551.
Research Article|
May 15 2018
Insulin-induced exocytosis regulates the cell surface level of low-density lipoprotein-related protein-1 in Müller Glial cells
Virginia Actis Dato;
Virginia Actis Dato
1Universidad Nacional de Córdoba, Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica, Córdoba, Argentina
2Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET),Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Córdoba, Argentina
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Rubén A. Grosso;
Rubén A. Grosso
3Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Histología y Embriología (IHEM), Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina
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María C. Sánchez;
María C. Sánchez
1Universidad Nacional de Córdoba, Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica, Córdoba, Argentina
2Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET),Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Córdoba, Argentina
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Claudio M. Fader;
Claudio M. Fader
3Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Histología y Embriología (IHEM), Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina
4Universidad Nacional de Cuyo, Facultad de Odontología, Mendoza, Argentina
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Gustavo A. Chiabrando
1Universidad Nacional de Córdoba, Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica, Córdoba, Argentina
2Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET),Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI), Córdoba, Argentina
Correspondence: Gustavo A. Chiabrando (gustavo.chiabrando@unc.edu.ar)
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Publisher: Portland Press Ltd
Received:
November 23 2017
Revision Received:
April 16 2018
Accepted:
April 17 2018
Accepted Manuscript online:
April 18 2018
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Biochem J (2018) 475 (9): 1669–1685.
Article history
Received:
November 23 2017
Revision Received:
April 16 2018
Accepted:
April 17 2018
Accepted Manuscript online:
April 18 2018
Citation
Virginia Actis Dato, Rubén A. Grosso, María C. Sánchez, Claudio M. Fader, Gustavo A. Chiabrando; Insulin-induced exocytosis regulates the cell surface level of low-density lipoprotein-related protein-1 in Müller Glial cells. Biochem J 15 May 2018; 475 (9): 1669–1685. doi: https://doi.org/10.1042/BCJ20170891
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