Ankyrin

Ankyrins are a family of adaptor proteins that mediate the attachment of integral membrane proteins to the spectrin-actin based membrane skeleton.^[1] Ankyrins have binding sites for the beta subunit of spectrin and at least 12 families of integral membrane proteins. This linkage is required to maintain the integrity of the plasma membranes and to anchor specific ion channels, ion exchangers and ion transporters in the plasma membrane.

Structure

Ankyrins contain four functional domains: an N-terminal domain that contains 24 tandem ankyrin repeats, a central domain that binds to spectrin, a death domain that is binds to proteins involved in apoptosis, and a C-terminal regulatory domain that is highly variable between different ankyrin proteins.^[1]

Subtypes

Ankyrins are encoded by three genes (ANK1, ANK2 and ANK3) in mammals. Each gene in turn produces multiple proteins through alternative splicing.

ANK1

The ANK1 gene encodes the AnkyrinR proteins. AnkyrinR was first characterized in human erythrocytes, where this ankyrin was referred to as erythrocyte ankyrin or band2.1.^[2] AnkyrinR erythrocytes to resist shear forces experienced in the circulation. Individuals with reduced or defective ankyrinR have a form of hemolytic anemia termed hereditary spherocytosis.^[3] In erythrocytes, AnkyrinR links the membrane skeleton to the Cl^-/HCO₃^- anion exchanger.^[4]

ANK2

Subsequently, ankyrinB proteins (products of the ANK2 gene^[6]) were identified in brain and muscle. AnkyrinB and AnkyrinG proteins are required for the polarized distribution of many membrane proteins including the Na⁺/K⁺ ATPase, the voltage gated Na⁺ channel and the Na⁺/Ca²⁺ exchanger.

ANK3

AnkyrinG proteins (products of the ANK3 gene^[7]) were identified in epithelial cells and neurons. A large-scale genetic analysis conducted in 2008 shows the possibility that ANK3 is involved in the bipolar disorder.^[8]^[9]

References

^ ^a ^b Bennett V, Baines AJ (July 2001). "Spectrin and ankyrin-based pathways: metazoan inventions for integrating cells into tissues". Physiol. Rev. 81 (3): 1353–92. PMID 11427698.
^ Bennett V, Stenbuck PJ (1979). "Identification and partial purification of ankyrin, the high affinity membrane attachment site for human erythrocyte spectrin". J Biol Chem 254 (7): 2533–41. PMID 372182.
^ Lux SE, Tse WT, Menninger JC, John KM, Harris P, Shalev O, Chilcote RR, Marchesi SL, Watkins PC, Bennett V (1990). "Hereditary spherocytosis associated with deletion of human erythrocyte ankyrin gene on chromosome 8". Nature 345 (6277): 736-9. doi:10.1038/345736a0. PMID 2141669.
^ Bennett V, Stenbuck PJ (1979). "The membrane attachment protein for spectrin is associated with band 3 in human erythrocyte membranes". Nature 280 (5722): 468-73. PMID 379653.
^ Singleton PA, Bourguignon LY (2004). "CD44 interaction with ankyrin and IP3 receptor in lipid rafts promotes hyaluronan-mediated Ca2+ signaling leading to nitric oxide production and endothelial cell adhesion and proliferation". Exp Cell Res 295 (1): 102–18. doi:10.1016/j.yexcr.2003.12.025. PMID 15051494.
^ Schott JJ, Charpentier F, Peltier S, et al (November 1995). "Mapping of a gene for long QT syndrome to chromosome 4q25-27". Am. J. Hum. Genet. 57 (5): 1114–22. PMID 7485162.
^ Kapfhamer D, Miller DE, Lambert S, Bennett V, Glover TW, Burmeister M (May 1995). "Chromosomal localization of the ankyrinG gene (ANK3/Ank3) to human 10q21 and mouse 10". Genomics 27 (1): 189–91. doi:10.1006/geno.1995.1023. PMID 7665168.
^ Ferreira MA, O'Donovan MC, Meng YA, et al (August 2008). "Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder". Nat. Genet.. doi:10.1038/ng.209. PMID 18711365.
^ "Channeling Mental Illness: GWAS Links Ion Channels, Bipolar Disorder". Schizophrenia Research Forum: News. schizophreniaforum.org (2008-08-19). Retrieved on 2008-08-21.

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