The role of the PTB daptor Anks1a in the COPII-mediated transport of EphA2 and ErbB2 receptors

Abstract

How the selective uptake of mature receptor tyrosine kinases (RTKs) from the ER is coupled to COPII carrier biogenesis is an issue that remains unresolved. In this report, we provide evidence that one of the phosphotyrosine binding (PTB) adaptors, Anks1a, is a protein localized to endoplasmic reticulum (ER). Down‐regulation of Anks1a impairs export of EphA2 RTK from the ER. Anks1a binds to EphA2 but also Sec23/24 complex to facilitate the loading of RTK cargo into a growing carrier. In this budding process, Anks1a does not enter the carrier. In breast tumor, EphA2 plays a role in increasing the protein level of ErbB2 through complex formation. Furthermore, ErbB2 requires both EphA2 and Anks1a for the export from the ER. Thus our findings reveal a unique mechanism to load mature RTKs into COPII carriers, which has an important implication in human diseases.