Deficiency of GABARAP but not its Paralogs Causes Enhanced EGF-induced EGFR Degradation

Cells

Sebastian Hänsch¹  JohannesG. Bode²  Kerstin Rufinatscha²  IndraM. Simons³  Dieter Willbold³  Jochen Dobner³  Thomas Gensch⁴  Iman Abdollahzadeh⁵  Melanie Schwarten⁵  Silke Hoffmann⁵  OliverH. Weiergräber⁵ 

[1] Department of Biology, Center for Advanced Imaging (CAi), Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany;Department of Gastroenterology, Hepatology and Infectiology, University Hospital, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany;Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany;Institute of Biological Information Processing: Molecular and Cell Physiology (IBI-1), Forschungszentrum Jülich, 52425 Jülich, Germany;Institute of Biological Information Processing: Structural Biochemistry (IBI-7), Forschungszentrum Jülich, 52425 Jülich, Germany;

关键词: EGFR;    GABARAP;    receptor trafficking;    degradation;    Atg8;    genome editing;   

DOI  :  10.3390/cells9051296

来源: DOAJ

【 摘 要 】

The γ-aminobutyric acid type A receptor-associated protein (GABARAP) and its close paralogs GABARAPL1 and GABARAPL2 constitute a subfamily of the autophagy-related 8 (Atg8) protein family. Being associated with a variety of dynamic membranous structures of autophagic and non-autophagic origin, Atg8 proteins functionalize membranes by either serving as docking sites for other proteins or by acting as membrane tethers or adhesion factors. In this study, we describe that deficiency for GABARAP alone, but not for its close paralogs, is sufficient for accelerated EGF receptor (EGFR) degradation in response to EGF, which is accompanied by the downregulation of EGFR-mediated MAPK signaling, altered target gene expression, EGF uptake, and EGF vesicle composition over time. We further show that GABARAP and EGFR converge in the same distinct compartments at endogenous GABARAP expression levels in response to EGF stimulation. Furthermore, GABARAP associates with EGFR in living cells and binds to synthetic peptides that are derived from the EGFR cytoplasmic tail in vitro. Thus, our data strongly indicate a unique and novel role for GABARAP during EGFR trafficking.

【 授权许可】

Unknown