ArticleMolecular and cellular biology2006
APPL1 associates with TrkA and GIPC1 and is required for nerve growth factor-mediated signal transduction.
Article in Molecular and cellular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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Who cites it
92 citing papers in PubMed.
- The power of five - inositol polyphosphate 5-phosphatase gene mutations at the intersection of development and disease.FEBS letters · 2026Review
- Increased Neuronal Expression of the Early Endosomal Adaptor APPL1 Replicates Alzheimer's Disease-Related Endosomal and Synaptic Dysfunction with Cholinergic Neurodegeneration.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- PDGFRα/β heterodimer activation negatively affects downstream ERK1/2 signaling and cellular proliferation.Nature communications · 2025Article
- Endosomal HAntioxidants (Basel, Switzerland) · 2025Article
- Article
- Neuron-secreted NLGN3 ameliorates ischemic brain injury via activating Gαi1/3-Akt signaling.Cell death & disease · 2023Article
- Review
- GIPC3 couples to MYO6 and PDZ domain proteins, and shapes the hair cell apical region.Journal of cell science · 2023Article
- GIPC3 couples to MYO6 and PDZ domain proteins and shapes the hair cell apical region.bioRxiv : the preprint server for biology · 2023Article
- G-alpha interacting protein interacting protein, C terminus 1 regulates epileptogenesis by increasing the expression of metabotropic glutamate receptor 7.CNS neuroscience & therapeutics · 2022Article
- Participation of OCRL1, and APPL1, in the expression, proteolysis, phosphorylation and endosomal trafficking of megalin: Implications for Lowe Syndrome.Frontiers in cell and developmental biology · 2022Article
- SH3BP4 promotes neuropilin-1 and α5-integrin endocytosis and is inhibited by Akt.Developmental cell · 2021Article
- Rapid whole cell imaging reveals a calcium-APPL1-dynein nexus that regulates cohort trafficking of stimulated EGF receptors.Communications biology · 2021Article
- Strength and duration of GIPC-dependent signaling networks as determinants in cancer.Neoplasia (New York, N.Y.) · 2021Review
- Recent advances in understanding gonadotropin signaling.Faculty reviews · 2021Review
- Mechanistic insight into how gonadotropin hormone receptor complexes direct signaling†.Biology of reproduction · 2020Review
- Pharmacological Programming of Endosomal Signaling Activated by Small Molecule Ligands of the Follicle Stimulating Hormone Receptor.Frontiers in pharmacology · 2020Article
- Article
- Retrograde transport of Akt by a neuronal Rab5-APPL1 endosome.Scientific reports · 2019Article
- A role for Regulator of G protein Signaling-12 (RGS12) in the balance between myoblast proliferation and differentiation.PloS one · 2019Article
32 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors.
Funding
Abstract
The neurotrophin receptor TrkA plays critical roles in the nervous system by recruiting signaling molecules that activate pathways required for the growth and survival of neurons. Here, we report APPL1 as a TrkA-associated protein. APPL1 and TrkA co-immunoprecipitated in sympathetic neurons. We have identified two routes through which this association can occur. APPL1 was isolated as a binding partner for the TrkA-interacting protein GIPC1 from rat brain lysate by mass spectrometry. The PDZ domain of GIPC1 directly engaged the C-terminal sequence of APPL1. This interaction provides a means through which APPL1 may be recruited to TrkA. In addition, the APPL1 PTB domain bound to TrkA, indicating that APPL1 may associate with TrkA independently of GIPC1. Isolation of endosomal fractions by high-resolution centrifugation determined that APPL1, GIPC1, and phosphorylated TrkA are enriched in the same fractions. Reduction of APPL1 or GIPC1 protein levels suppressed nerve growth factor (NGF)-dependent MEK, extracellular signal-regulated kinase, and Akt activation and neurite outgrowth in PC12 cells. Together, these results indicate that GIPC1 and APPL1 play a role in TrkA function and suggest that a population of endosomes bearing a complex of APPL1, GIPC1, and activated TrkA may transmit NGF signals.
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