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ATM binds to beta-adaptin in cytoplasmic vesicles
D S Lim1, D G Kirsch, C E Canman
1Oncology Center, The Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Abstract:
Inherited mutations in the ATM gene lead to a complex clinical phenotype characterized by neuronal degeneration, oculocutaneous telangiectasias, immune dysfunction, and cancer predisposition. Using the yeast two-hybrid system, we demonstrate that ataxia telangiectasia mutated (ATM) binds to beta-adaptin, one of the components of the AP-2 adaptor complex, which is involved in clathrin-mediated endocytosis of receptors. The interaction between ATM and beta-adaptin was confirmed in vitro, and coimmunoprecipitation and colocalization studies show that the proteins also associate in vivo. ATM also interacts in vitro with beta-NAP, a neuronal-specific beta-adaptin homolog that was identified as an autoantigen in a patient with cerebellar degeneration. Our data describing the association of ATM with beta-adaptin in vesicles indicate that ATM may play a role in intracellular vesicle and/or protein transport mechanisms.
Insights
Ataxia telangiectasia mutated (ATM) protein interacts with beta-adaptin, a key component in cellular transport. This finding suggests ATM’s role in intracellular vesicle and protein transport mechanisms.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Inherited ATM gene mutations cause ataxia telangiectasia, a disorder with neurological, immunological, and cancer-related symptoms.
- The ATM protein's precise cellular functions beyond DNA repair are not fully understood.
Purpose of the Study:
- To investigate potential novel interactions of the ATM protein within cellular pathways.
- To explore ATM's role in intracellular trafficking and protein transport.
Main Methods:
- Yeast two-hybrid screening to identify ATM-interacting proteins.
- In vitro binding assays to confirm interactions.
- Coimmunoprecipitation and colocalization studies to validate in vivo association.
Main Results:
- ATM directly binds to beta-adaptin, a component of the AP-2 clathrin-mediated endocytosis complex.
- ATM also interacts with beta-NAP, a neuronal beta-adaptin homolog.
- ATM and beta-adaptin co-localize within cellular vesicles, indicating a functional association.
Conclusions:
- ATM associates with beta-adaptin and beta-NAP, suggesting a role in vesicle-mediated transport.
- These findings implicate ATM in intracellular protein and vesicle trafficking pathways, potentially linking its function to neuronal degeneration observed in ataxia telangiectasia.