Transthyretin binds to glucose-regulated proteins and is subjected to endocytosis by the pancreatic β-cell

被引:0
作者
Nancy Dekki
Essam Refai
Rebecka Holmberg
Martin Köhler
Hans Jörnvall
Per-Olof Berggren
Lisa Juntti-Berggren
机构
[1] Karolinska Institutet,The Rolf Luft Research Center for Diabetes and Endocrinology
[2] Karolinska University Hospital L1:03,Department of Medical Biochemistry and Biophysics
[3] Karolinska Institutet,undefined
来源
Cellular and Molecular Life Sciences | 2012年 / 69卷
关键词
Transthyretin; Pancreatic β-cell; Glucose-regulated proteins; Dynasore; Surface plasmon resonance;
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摘要
Transthyretin (TTR) is a functional protein in the pancreatic β-cell. It promotes insulin release and protects against β-cell death. We now demonstrate by ligand blotting, adsorption to specific magnetic beads, and surface plasmon resonance that TTR binds to glucose-regulated proteins (Grps)78, 94, and 170, which are members of the endoplasmic reticulum chaperone family, but Grps78 and 94 have also been found at the plasma membrane. The effect of TTR on changes in cytoplasmic free Ca2+ concentration ([Ca2+]i) was abolished if the cells were treated with either dynasore, a specific inhibitor of dynamin GTPase that blocks clathrin-mediated endocytosis, or an antibody against Grp78, that prevents TTR from binding to Grp78. The conclusion is that TTR binds to Grp78 at the plasma membrane, is internalized into the β-cell via a clathrin-dependent pathway, and that this internalization is necessary for the effects of TTR on β-cell function.
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页码:1733 / 1743
页数:10
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