Identification of the soluble EphA7-interacting protein Nicalin as a regulator of EphA7 expression
- PDF / 2,470,334 Bytes
- 8 Pages / 595.276 x 790.866 pts Page_size
- 89 Downloads / 192 Views
Identification of the soluble EphA7‑interacting protein Nicalin as a regulator of EphA7 expression Xiaolei Wang2 · Zhaobao Wang1 Received: 8 June 2020 / Accepted: 2 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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. Keywords Nicalin · sEphA7 · EphA7-FL · Antagonistic mechanism
Introduction Members of the Eph family of receptor tyrosine kinases are widely expressed during embryonic development and play crucial roles in boundary formation, morphogenesis, angiogenesis, and tissue patterning [1–3]. Eph receptors can be classified into two groups: EphAs which typically bind GPIanchored ephrinA ligands, and EphBs, which typically bind transmembranous ephrinB ligands [4]. EphA7 is a member of the EphA receptors, involved in hindbrain, pronephros, and otocyst development in Xenopus [5–7]. A soluble form Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11010-020-03898-1) contains supplementary material, which is available to authorized users. * Zhaobao Wang [email protected] 1
School of Control Science and Engineering, Shandong University, 17923 Jingshi Road, Jinan 250061, China
State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, China
2
of EphA7 (sEphA7) has been widely reported to function as a tumor suppressor in lymphomas and lung cancer tissues [8–10]. Our previous study demonstrated that sEphA7 antagonizes the role of full-length EphA7 (EphA7-FL) to stabilize the membrane level of the tight junction protein Claudin6 (CLDN6) in Xenopus pronephros development [6]. However, the mechanism und
Data Loading...
