Background: AP2 is a clathrin-based endocytic adaptor complex comprising α, β2, μ2 and σ2 subunits. μ2 regulates CFTR endocytosis. The α subunit interacts with CFTR in the intestine but its physiologic significance is unclear.
Methods: CFTR short circuit current was measured in intestinal T84 cells following shRNA knock down of AP2α (AP2αKD). Clathrin-coated structures (CCS) were immunolabeled and quantified in AP2αKD intestinal Caco2BBe (C2BBe) cells. GST tagged human AP2α appendage domain was cloned and its interaction with CFTR determined by GST pull down assay.
Result: AP2αKD in T84 cells resulted in higher CFTR current (57%) compared to control, consistent with increased functional CFTR and delayed endocytosis. Depletion of AP2α reduced CCS in C2BBe cells. Pull down assays revealed an interaction between human AP2α appendage domain and CFTR.
Conclusion: AP2 α interacts with and modulates CFTR function in the intestine by participating in clathrin assembly and recruitment of CFTR to CCS.
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| http://dx.doi.org/10.1016/j.jcf.2017.03.012 | DOI Listing |
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