Disease relevance of Ank3

• Fine genetic map of mouse chromosome 10 around the polycystic kidney disease gene, jcpk, and ankyrin 3 [1].

High impact information on Ank3

• We have recently cloned and characterized ankyrin-3 (also called ankyrin(G)), a new ankyrin that is widely distributed, especially in epithelial tissues, muscle, and neuronal axons (Peters, L.L., K.M. John, F.M. Lu, E.M. Eicher, A. Higgins, M. Yialamas, L.C. Turtzo, A.J. Otsuka, and S.E. Lux. 1995. J. Cell Biol. 130: 313-330) [2].
• Isoforms of ankyrin-3 that lack the NH2-terminal repeats associate with mouse macrophage lysosomes [2].
• Second, the ankyrin-3-positive vesicles contain lysosomal-associated membrane glycoprotein (LAMP-1), a recognized lysosomal marker [2].
• Also, epitope-tagged mouse macrophage ankyrin-3, transiently expressed in COS cells, associates with intracellular, not plasma, membranes [2].
• Here we show that in mouse macrophages, ankyrin-3 is expressed exclusively as two small isoforms (120 and 100 kD) that lack the NH2-terminal repeats [2].

Biological context of Ank3

• The jcpk intercross allowed the orientation of the Ank3 gene relative to the centromere to be determined [1].

Anatomical context of Ank3

• Ank3 is diffusely distributed in some or all cells and may be associated with cytoplasmic structures [3].
• These proximal vs. distal differences in Ank3 spliceoforms were displayed in LLC-PK1 cells, a proximal cell line, and MDCK cells, a distal cell line [4].
• Third, Na/K-ATPase, ankyrin-3, and fodrin specifically colocalize at the basal-lateral plasma membrane of all epithelial cells in which they are expressed and during all stages of nephrogenesis [5].
• Both alpha subunits of the Na,K-ATPase colocalize with beta-spectrin and ankyrin 3 in costameres, structures at the sarcolemma that lie over Z and M-lines and in longitudinal strands [6].

Other interactions of Ank3

• The Ank3 gene maps to mouse Chromosome 10, approximately 36 cM from the centromere, a locus distinct from Ank1 and Ank2 [3].
• In immunoprecipitates, the alpha1 and alpha2 subunits of the Na,K-ATPase as well as ankyrin 3 associate with beta-spectrin/alpha- fodrin heteromers and with a pool of beta-spectrin at the sarcolemma that does not contain alpha-fodrin [6].

Analytical, diagnostic and therapeutic context of Ank3

• The ankyrin-3-positive vesicles appear dark on phase-contrast microscopy [2].
• Fourth, the relative immunofluorescence staining intensities of Na/K-ATPase, ankyrin-3, and fodrin become more similar during development until they are essentially identical in adult kidney [5].

1. Fine genetic map of mouse chromosome 10 around the polycystic kidney disease gene, jcpk, and ankyrin 3. Bryda, E.C., Ling, H., Rathbun, D.E., Burmeister, M., Flaherty, L. Genomics (1996)
2. Isoforms of ankyrin-3 that lack the NH2-terminal repeats associate with mouse macrophage lysosomes. Hoock, T.C., Peters, L.L., Lux, S.E. J. Cell Biol. (1997)
3. Ank3 (epithelial ankyrin), a widely distributed new member of the ankyrin gene family and the major ankyrin in kidney, is expressed in alternatively spliced forms, including forms that lack the repeat domain. Peters, L.L., John, K.M., Lu, F.M., Eicher, E.M., Higgins, A., Yialamas, M., Turtzo, L.C., Otsuka, A.J., Lux, S.E. J. Cell Biol. (1995)
4. Distribution of epithelial ankyrin (Ank3) spliceoforms in renal proximal and distal tubules. Doctor, R.B., Chen, J., Peters, L.L., Lux, S.E., Mandel, L.J. Am. J. Physiol. (1998)
5. Biogenesis of polarized epithelial cells during kidney development in situ: roles of E-cadherin-mediated cell-cell adhesion and membrane cytoskeleton organization. Piepenhagen, P.A., Nelson, W.J. Mol. Biol. Cell (1998)
6. Na,K-ATPase in skeletal muscle: two populations of beta-spectrin control localization in the sarcolemma but not partitioning between the sarcolemma and the transverse tubules. Williams, M.W., Resneck, W.G., Kaysser, T., Ursitti, J.A., Birkenmeier, C.S., Barker, J.E., Bloch, R.J. J. Cell. Sci. (2001)