|Manohar, Murli -|
|Mei, Hui -|
|Franklin, Andrew -|
|Sweet, Elly -|
|Shigaki, Toshiro -|
|Riley, Bruce -|
|Macdiarmid, Colin -|
|Hirschi, Kendal -|
Submitted to: Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: June 7, 2010
Publication Date: June 25, 2010
Repository URL: http://pubs.acs.org.ezproxyhost.library.tmc.edu/toc/bichaw/49/31
Citation: Manohar, M., Mei, H., Franklin, A.J., Sweet, E.M., Shigaki, T., Riley, B.B., MacDiarmid, C.W., Hirschi, K. 2010. Zebrafish ("Danio rerio") endomembrane antiporter similar to a yeast cation/H(+) transporter is required for neural crest development. Biochemistry. 49(31):6557-6566. Interpretive Summary: Plants and animals differ in many important aspects. For example, plants are rooted in one place while most animals have the ability to move. The ability to move, or adapt to the environment often requires plants and animals to both respond by changing the intracellular concentration of calcium in cells. Cation exchangers (CAXs) are an important type of calcium transporter that move calcium in plants cells, but were thought to be absent from animals. Here we characterize the first CAX from animals. We demonstrate that in fish, this CAX appears to be important for neural development. Collectively, our findings provide insights into the role of CAX transporters and provide opportunity to further understand the commonalities among plants and animals.
Technical Abstract: CAtion/H (+) eXchangers (CAXs) are integral membrane proteins that transport Ca (2+) or other cations by exchange with protons. While several yeast and plant CAX proteins have been characterized, no functional analysis of a vertebrate CAX homologue has yet been reported. In this study, we further characterize a CAX from yeast, VNX1, and initiate characterization of a zebra fish CAX (Cax1). Localization studies indicated that both Vnx1 and Cax1 proteins are found in endomembrane compartments. Biochemical characterization of endomembrane fractions from vnx1 mutant cells and zebra fish Cax1-expressing yeast cells suggested that both yeast and fish CAXs have Ca(2+)/H(+) antiport activities. Additionally, the vnx1 mutation was associated with heightened pH-sensitivity. In zebra fish embryos, cax1 was specifically expressed in neural crest cells. Morpholino knockdown of cax1 caused defects in neural crest development, including alterations in pigmentation, defects in jaw development, and reduction in expression of the neural crest marker, Pax7. Collectively, our findings provide insights into Vnx1 function and support an unexpected role of CAX transporters in animal growth and development.