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Molecular Biology of the Cell
Article
License: CC BY NC SA
Data sources: UnpayWall
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PubMed Central
Other literature type . 2015
Data sources: PubMed Central
Molecular Biology of the Cell
Article . 2015 . Peer-reviewed
Data sources: Crossref
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GGA3 mediates TrkA endocytic recycling to promote sustained Akt phosphorylation and cell survival

Authors: Li, Xuezhi; Lavigne, Pierre; Lavoie, Christine;

GGA3 mediates TrkA endocytic recycling to promote sustained Akt phosphorylation and cell survival

Abstract

Although TrkA postendocytic sorting significantly influences neuronal cell survival and differentiation, the molecular mechanism underlying TrkA receptor sorting in the recycling or degradation pathways remains poorly understood. Here we demonstrate that Golgi-localized, γ adaptin-ear–containing ADP ribosylation factor-binding protein 3 (GGA3) interacts directly with the TrkA cytoplasmic tail through an internal DXXLL motif and mediates the functional recycling of TrkA to the plasma membrane. We find that GGA3 depletion by siRNA delays TrkA recycling, accelerates TrkA degradation, attenuates sustained NGF-induced Akt activation, and reduces cell survival. We also show that GGA3’s effect on TrkA recycling is dependent on the activation of Arf6. This work identifies GGA3 as a key player in a novel DXXLL-mediated endosomal sorting machinery that targets TrkA to the plasma membrane, where it prolongs the activation of Akt signaling and survival responses.

Related Organizations
Keywords

Cell Survival, Golgi Apparatus, Endosomes, PC12 Cells, Cell Movement, Animals, Humans, Amino Acid Sequence, Phosphorylation, Receptor, trkA, ADP-Ribosylation Factors, Cell Membrane, Biological Transport, Articles, Rats, Oncogene Protein v-akt, Adaptor Proteins, Vesicular Transport, Protein Transport, HEK293 Cells, ADP-Ribosylation Factor 6, Protein Binding

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    citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    22
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Average
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
22
Top 10%
Average
Top 10%
Green
hybrid