Ankyrin-B is required for coordinated expression of beta-2-spectrin, the Na/K-ATPase and the Na/Ca exchanger in the inner segment of rod photoreceptors.
Rod photoreceptors are highly polarized cells whose exquisite sensitivity to light depends on precise compartmentalization of ion channels/transporters within specialized membrane domains. Here, we report evidence for an ankyrin-B based mechanism for coordinated expression of the beta-2-spectrin-based membrane skeleton, and the Na/K-ATPase and Na/Ca exchanger in the inner segment of rod photoreceptors. We first discovered that ankyrin-B localizes to the inner segments but not outer segments of rod photoreceptors in vertebrates including humans, mice, and frogs. We found that haploinsufficiency of ankyrin-B in mice is accompanied by 50% reduction in inner segments of membrane proteins, including the Na/K-ATPase and the Na/Ca exchanger, as well as beta-2-spectrin, which is a component of the spectrin-actin membrane skeleton. These results are consistent with a mechanism where ankyrin-B is required to restrict the Na/K-ATPase and Na/Ca exchanger to the inner segment of rod photoreceptors by tethering these membrane proteins to beta-2-spectrin.
Kizhatil
Krishnakumar
K
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA. k.kizhatil@cellbio.duke.edu
Sandhu
Nina K
NK
Peachey
Neal S
NS
Bennett
Vann
V
D000818:Animals; D017487:Ankyrins / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism*; D004596:Electroretinography; D005136:Eye Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism*; D055211:Retinal Photoreceptor Cell Inner Segment / Q000378:metabolism* / Q000502:physiology; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013045:Species Specificity; D014981:Xenopus; D013049:Spectrin
D017487:Ankyrins; D002352:Carrier Proteins; D005136:Eye Proteins; D008840:Microfilament Proteins; D019831:Sodium-Calcium Exchanger; D000254:Sodium-Potassium-Exchanging ATPase; D013049:Spectrin; C498994:ANK2 protein, human; C498995:Ank2 protein, mouse