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Mol Cell Biochem
2021 Jan 01;4761:213-220. doi: 10.1007/s11010-020-03898-1.
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Identification of the soluble EphA7-interacting protein Nicalin as a regulator of EphA7 expression.
Wang X
,
Wang Z
.
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A soluble form of EphA7 (sEphA7) has been found to antagonize the role of full-length EphA7 (EphA7-FL) to stabilize the membrane level of the tight junction protein Claudin6 (CLDN6) during Xenopus pronephros development. However, the mechanism underlying this antagonistic effect remains unclear. In this study, we identified Nicalin, a Nicastrin-like protein, as a novel sEphA7-interacting protein using immunoprecipitation (IP)/mass spectrometry (MS). In HEK293 cells, Nicalin interacted with sEphA7 and they predominantly co-localized in the endoplasmic reticulum (ER). Interestingly, Nicalin diminished the protein level of sEphA7 in the membranous fraction but increased that in the insoluble cytoplasmic fraction with a reduced molecular weight, suggesting that Nicalin restricts the entry of sEphA7 into the ER for further modification. sEphA7 probably acted as a chaperone and enhanced the membrane level of EphA7-FL and the formation of EphA7 complex, however, this effect was reversed by Nicalin. Our work suggested that Nicalin limits sEphA7 secretion, thereby preventing the formation of EphA7 complex. These results demonstrated the potential role of Nicalin in regulating EphA7 expression and revealed a potential mechanism underlying the antagonistic effect between sEphA7 and EphA7-FL.
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