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

This title appears in the Scientific Report : 2020

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

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...

Personal Name(s):	Dobner, Jochen
	Simons, Indra M. / Rufinatscha, Kerstin / Hänsch, Sebastian / Schwarten, Melanie / Weiergräber, Oliver H. / Abdollahzadeh, Iman / Gensch, Thomas / Bode, Johannes G. / Hoffmann, Silke / Willbold, Dieter (Corresponding author)
Contributing Institute:	Strukturbiochemie; IBI-7
Published in:	Cells, 9 (2020) 5, S. 1296 -
Imprint:	Basel MDPI 2020
DOI:	10.3390/cells9051296
PubMed ID:	32456010
Document Type:	Journal Article
Research Program:	Physical Basis of Diseases
Link:	Get full text Get full text OpenAccess OpenAccess
	Publikationsportal JuSER

Please use the identifier: http://dx.doi.org/10.3390/cells9051296 in citations.
Please use the identifier: http://hdl.handle.net/2128/25098 in citations.

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.