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Ankyrin-3

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Ankyrin-3 (ANK-3), also known as ankyrin-G, is a protein from ankyrin family that in humans is encoded by the ANK3 gene.[1][2]

Function

The protein encoded by this gene, ankyrin-3 is an immunologically distinct gene product from ankyrins ANK1 and ANK2, and was originally found at the axonal initial segment and nodes of Ranvier of neurons in the central and peripheral nervous systems. Alternatively spliced variants may be expressed in other tissues. Although multiple transcript variants encoding several different isoforms have been found for this gene, the full-length nature of only two have been characterized.[1]

Within the nervous system, ankyrin-G is specifically localized to the neuromuscular junction, the axon initial segment and the Nodes of Ranvier.[3] Within the nodes of Ranvier where action potentials are actively propagated, ankyrin-G has long been thought to be the intermediate binding partner to neurofascin and voltage-gated sodium channels.[4] The genetic deletion of ankyrin-G from multiple neuron types has shown that ankyrin-G is required for the normal clustering of voltage-gated sodium channels at the axon hillock and for action potential firing.[5][6]

Disease linkage

The ANK3 protein associates with the cardiac sodium channel Nav1.5 (SCN5A). Both proteins are highly expressed at ventricular intercalated disc and T-tubule membranes in cardiomyocytes. A mutation in the Nav1.5 protein blocks interaction with ANK3 binding and therefore disrupts surface expression of Nav1.5 in cardiomyocytes resulting in Brugada syndrome, a type of cardiac arrhythmia.[7]

Other mutations in the ANK3 gene may be involved in the bipolar disorder and intellectual disability.[8][9][10][11]

Ankyrin family

The protein encoded by the ANK3 gene is a member of the ankyrin family of proteins that link the integral membrane proteins to the underlying spectrin-actin cytoskeleton. Ankyrins play key roles in activities such as cell motility, activation, proliferation, contact and the maintenance of specialized membrane domains. Most ankyrins are typically composed of three structural domains: an amino-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin binding domain; and a carboxy-terminal regulatory domain which is the least conserved and subject to variation.[1]

References

  1. ^ a b c "Entrez Gene: ANK2 ankyrin 3, node of Ranvier".
  2. ^ Kapfhamer D, Miller DE, Lambert S, Bennett V, Glover TW, Burmeister M (May 1995). "Chromosomal localization of the ankyrin-G gene (ANK3/Ank3) to human 10q21 and mouse 10". Genomics. 27 (1): 189–91. doi:10.1006/geno.1995.1023. PMID 7665168.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  3. ^ Lambert S, Davis JQ, Bennett V (September 1997). "Morphogenesis of the node of Ranvier: co-clusters of ankyrin and ankyrin-binding integral proteins define early developmental intermediates". J Neurosci. 17 (18): 7025–36. PMID 9278538.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ Srinivasan Y, Lewallen M, Angelides KJ (April 1992). "Mapping the binding site on ankyrin for the voltage-dependent sodium channel from brain". J Biol Chem. 267 (11): 7483–9. PMID 1313804.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ^ Zhou D, Lambert S, Malen PL, Carpenter S, Boland LM, Bennett V (November 1998). "AnkyrinG Is Required for Clustering of Voltage-gated Na Channels at Axon Initial Segments and for Normal Action Potential Firing". J Cell Biol. 143 (5): 1295–1304. doi:10.1083/jcb.143.5.1295. PMC 2133082. PMID 9832557.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  6. ^ Hedstrom KL, Xu X, Ogawa Y, Frischknecht R, Seidenbecher CI, Shrager P, Rasband MN (August 2007). "Neurofascin assembles a specialized extracellular matrix at the axon initial segment". J Cell Biol. 178 (5): 875–886. doi:10.1083/jcb.200705119. PMC 2064550. PMID 17709431.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  7. ^ Mohler PJ, Rivolta I, Napolitano C, LeMaillet G, Lambert S, Priori SG, Bennett V (December 2004). "Nav1.5 E1053K mutation causing Brugada syndrome blocks binding to ankyrin-G and expression of Nav1.5 on the surface of cardiomyocytes". Proc. Natl. Acad. Sci. U.S.A. 101 (50): 17533–8. doi:10.1073/pnas.0403711101. PMC 536011. PMID 15579534.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ^ http://www.yumanewsnow.com/index.php/news/health/8847-bipolar-disorder-discovery-at-the-nano-level
  9. ^ 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. 40 (9): 1056–8. doi:10.1038/ng.209. PMC 2703780. PMID 18711365. {{cite journal}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  10. ^ "Channeling Mental Illness: GWAS Links Ion Channels, Bipolar Disorder". Schizophrenia Research Forum: News. schizophreniaforum.org. 2008-08-19. Retrieved 2008-08-21.
  11. ^ Iqbal, Zafar; Vandeweyer, Geert; van der Voet, Monique; Waryah, Ali Muhammad; Zahoor, Muhammad Yasir; Besseling, Judith A.; Roca, Laura Tomas; Vulto-van Silfhout, Anneke T.; Nijhof, Bonnie; Kramer, Jamie M.; Van der Aa, Nathalie; Ansar, Muhammad; Peeters, Hilde; Helsmoortel, Celine; Gilissen, Christian; Vissers, Lisenka; Veltman, Joris A.; de Brouwer, Arjan P. M.; Kooy, R. Frank; Riazuddin, Sheikh; Schenck, Annette; van Bokhoven, Hans; Rooms, Liesbeth (2013). "Homozygous and heterozygous disruptions of ANK3: at the crossroads of neurodevelopmental and psychiatric disorders". Human Molecular Genetics. 22: 1960–1970. doi:10.1093/hmg/ddt043. ISSN 0964-6906.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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