scholarly journals Native adiponectin in serum binds to mammalian cells expressing T-cadherin, but not AdipoRs or calreticulin

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Shunbun Kita ◽  
Shiro Fukuda ◽  
Norikazu Maeda ◽  
Iichiro Shimomura
Keyword(s):  
Cell Surface ◽  
Human Serum ◽  
Cho Cells ◽  
Mammalian Cells ◽  
Hek293 Cells ◽  
C2c12 Myotubes ◽  
Binding Partner ◽  
Surface Localization ◽  
Significant Attenuation ◽  
Cell Surface Localization

Adiponectin is an adipocyte-derived atypically abundant circulating factor that protects various organs and tissues through its receptors, AdipoRs, calreticulin, and T-cadherin. To identify the major binding partner of circulating native adiponectin, we expressed these receptors on the surface of HEK293 cells. Adiponectin, either that in mouse or human serum, purified from serum, or produced by mammalian cells, bound to cells expressing T-cadherin, but not to those expressing AdipoR1 or calreticulin. The stable introduction of T-cadherin and AdipoR1 into CHO cells resulted in the cell surface localization of these receptors. Native adiponectin in serum bound to cells expressing T-cadherin, not to those expressing AdipoR1. The knockdown of T-cadherin, but not AdipoRs resulted in the significant attenuation of native adiponectin binding to C2C12 myotubes. Therefore, native adiponectin binding depended on the amount of T-cadherin expressed in HEK293 cells, CHO cells, and C2C12 myotubes. Collectively, our mammalian cell-based studies suggest that T-cadherin is the major binding partner of native adiponectin in serum.

scholarly journals A novel motif in the proximal C-terminus of Pannexin 1 regulates cell surface localization

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Anna L. Epp ◽  
Sarah N. Ebert ◽  
Juan C. Sanchez-Arias ◽  
Leigh E. Wicki-Stordeur ◽  
Andrew K. J. Boyce ◽  
...  
Keyword(s):  
Cell Surface ◽  
Pannexin 1 ◽  
C Terminus ◽  
Surface Localization ◽  
Cell Surface Localization

scholarly journals Cell Surface Localization of Proteolysis of Human Endothelial Angiotensin I-converting Enzyme

1995 ◽  
Vol 270 (48) ◽  
pp. 28962-28969 ◽  
Author(s):  
Véronique Beldent ◽  
Annie Michaud ◽  
Christophe Bonnefoy ◽  
Marie-Thérèse Chauvet ◽  
Pierre Corvol
Keyword(s):  
Cell Surface ◽  
Converting Enzyme ◽  
Angiotensin I ◽  
Angiotensin I Converting Enzyme ◽  
Surface Localization ◽  
Cell Surface Localization

scholarly journals An essential role for the Glut1 PDZ-binding motif in growth factor regulation of Glut1 degradation and trafficking

2009 ◽  
Vol 418 (2) ◽  
pp. 345-367 ◽  
Author(s):  
Heather L. Wieman ◽  
Sarah R. Horn ◽  
Sarah R. Jacobs ◽  
Brian J. Altman ◽  
Sally Kornbluth ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Surface ◽  
Glucose Uptake ◽  
Pdz Domain ◽  
Binding Motif ◽  
Lysosomal Degradation ◽  
Interacting Protein ◽  
Surface Localization ◽  
Cell Surface Localization ◽  
Growth Factor Regulation

Cell surface localization of the Glut (glucose transporter), Glut1, is a cytokine-controlled process essential to support the metabolism and survival of haemopoietic cells. Molecular mechanisms that regulate Glut1 trafficking, however, are not certain. In the present study, we show that a C-terminal PDZ-binding motif in Glut1 is critical to promote maximal cytokine-stimulated Glut1 cell surface localization and prevent Glut1 lysosomal degradation in the absence of growth factor. Disruption of this PDZ-binding sequence through deletion or point mutation sharply decreased surface Glut1 levels and led to rapid targeting of internalized Glut1 to lysosomes for proteolysis, particularly in growth factor-deprived cells. The PDZ-domain protein, GIPC (Gα-interacting protein-interacting protein, C-terminus), bound to Glut1 in part via the Glut1 C-terminal PDZ-binding motif, and we found that GIPC deficiency decreased Glut1 surface levels and glucose uptake. Unlike the Glut1 degradation observed on mutation of the Glut1 PDZ-binding domain, however, GIPC deficiency resulted in accumulation of intracellular Glut1 in a pool distinct from the recycling pathway of the TfR (transferrin receptor). Blockade of Glut1 lysosomal targeting after growth factor withdrawal also led to intracellular accumulation of Glut1, a portion of which could be rapidly restored to the cell surface after growth factor stimulation. These results indicate that the C-terminal PDZ-binding motif of Glut1 plays a key role in growth factor regulation of glucose uptake by both allowing GIPC to promote Glut1 trafficking to the cell surface and protecting intracellular Glut1 from lysosomal degradation after growth factor withdrawal, thus allowing the potential for a rapid return of intracellular Glut1 to the cell surface on restimulation.

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