ABSTRACT
ATP8A2 is a P4-ATPase that is highly expressed in the retina, brain, spinal cord and testes. In the retina, ATP8A2 is localized in photoreceptors where it uses ATP to transport phosphatidylserine (PS) and phosphatidylethanolamine (PE) from the exoplasmic to the cytoplasmic leaflet of membranes. Although mutations in ATP8A2 have been reported to cause mental retardation in humans and degeneration of spinal motor neurons in mice, the role of ATP8A2 in sensory systems has not been investigated. We have analyzed the retina and cochlea of ATP8A2-deficient mice to determine the role of ATP8A2 in visual and auditory systems. ATP8A2-deficient mice have shortened photoreceptor outer segments, a reduction in photoresponses and decreased photoreceptor viability. The ultrastructure and phagocytosis of the photoreceptor outer segment appeared normal, but the PS and PE compositions were altered and the rhodopsin content was decreased. The auditory brainstem response threshold was significantly higher and degeneration of spiral ganglion cells was apparent. Our studies indicate that ATP8A2 plays a crucial role in photoreceptor and spiral ganglion cell function and survival by maintaining phospholipid composition and contributing to vesicle trafficking.
Footnotes
↵* These authors contributed equally to this work.
Competing interests
The authors declare no competing interests.
Author contributions
J.A.C., X.Z., H.R.D., L.L.M., R.S.S., R.T.L. carried out the experiments. J.A.C., X.Z., R.S.M. and S.W.M.J. designed the experiments. J.A.C., R.S.M. and S.W.M.J. wrote the manuscript.
Funding
This work was supported by grants from the Canadian Institutes for Health Research [grant number MOP-106667 to R.S.M.]; the National Institutes of Health [grant number EY02422 to R.S.M.; EY11721 to S.W.M.J.]; Pew Charitable Trust [S.W.M.J.]; National Science Foundation of China [grant number 81271007 to X.Z.]. J.A.C. was supported by a National Sciences and Engineering Council predoctoral studentship. R.S.M. holds a Canada Research Chair in Vision and Macular Degeneration. S.W.M.J. is an Investigator of the Howard Hughes Medical Institute. Deposited in PMC for release after 6 months.
Supplementary material available online at http://jcs.biologists.org/lookup/suppl/doi:10.1242/jcs.145052/-/DC1
- Received October 21, 2013.
- Accepted December 6, 2013.
- © 2014. Published by The Company of Biologists Ltd
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