A caveolin binding motif in Na/K-ATPase is required for stem cell differentiation and organogenesis in mammals and C.elegans
Authors: Guo-Zhang Zhu
Xiaoyu Cui
Yiliang Chen
Zijian Xie
Liquan Cai
Xiaoliang Wang
Jeffrey X Xie
Sandrine V Pierre
Dianqing Wu
Jue Zhang
Isabel Larre
Jiayan Wang
Joseph I Shapiro
Journal: Science Advances (2020)
Discipline: Multidisciplinary
Keywords: signaling events; cell lineage specification; organogenesis; caveolin binding motif (CBM); Na/K-adenosine triphosphatase (ATPase) (NKA)
Affiliations: Marshall Institute for Interdisciplinary Research (MIIR) at Marshall University, Huntington, WV, USA., University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA., Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI, USA., Joan C. Edwards School of Medicine at Marshall University, Huntington, WV, USA., Department of Pharmacology and Vascular Biology and Therapeutics, Yale School of Medicine, New Haven, CT, USA., Department of Biological Sciences, Marshall University, Huntington, WV, USA.

Abstract:  Several signaling events have been recognized as essential for regulating cell lineage specification and organogenesis in animals. We find that the gain of an amino-terminal caveolin binding motif (CBM) in the α subunit of the Na/K-adenosine triphosphatase (ATPase) (NKA) is required for the early stages of organogenesis in both mice and Caenorhabditis elegans. The evolutionary gain of the CBM occurred at the same time as the acquisition of the binding sites for Na+/K+. Loss of this CBM does not affect cell lineage specification or the initiation of organogenesis, but arrests further organ development. Mechanistically, this CBM is essential for the dynamic operation of Wnt and the timely up-regulation of transcriptional factors during organogenesis. These results indicate that the NKA was evolved as a dual functional protein that works in concert with Wnt as a hitherto unrecognized common mechanism to enable stem cell differentiation and organogenesis in multicellular organisms within the animal kingdom. 

Retracted: No

PubPeer comments:
 ![file] FIG 3E. WT results are very similar to the alpha 1 , 
 #1 Yes, with enhanced brightness common background features are visible; these images appear to be the same. **![file] , 
 I will share with the first (and corresponding) author. , 
 Dear Elasmolomus Pallens and PubPeer, Thank you very much for pointing out this mistake. We made a mistake by duplicate a NKA alpha1 heterozygous image and presented as wild-type. I attached the raw images for your to review. In the mean time, I will contact the journal to fix this mistake. Thank you very much again! Best Xiaoliang ![file] ![file] , 
 Dear Actinopolyspora Biskrensis and PubPeer, Thank you very much for pointing out this mistake in our paper. We made a mistake by duplicate a NKA alpha1 heterozygous image and presented as wild-type. I attached the raw images for your to review, I can also provide each images separately for you if you want. In the mean time, I will contact the journal to fix this mistake. Thank you very much again! Best Xiaoliang , 
 #4 And the correct image of the WT embryo? , 
 #6 The NKA a1 (+ +) means wild-type, we will replace on from the raw data. , 
 #7 Thanks for clarification. ,