Aladin (protein) explained

Aladin, also known as adracalin, is a nuclear envelope protein that in humans is encoded by the AAAS gene.^[1] It is named after the achalasia–addisonianism–alacrima syndrome (triple A syndrome) which occurs when the gene is mutated.

Function

Aladin is a component of the nuclear pore complex, to which it is attached by nucleoporin NDC1.^{[2] [3]} Mutant aladin causes selective failure of nuclear protein import and hypersensitivity to oxidative stress.^[4] Mutant aladin also causes decreased nuclear import of aprataxin, a repair protein for single-strand breaks, and DNA ligase I, employed in DNA base excision repair. These decreases in DNA repair proteins may increase the susceptibility of cells to oxidative stress by allowing accumulation of oxidative DNA damages that trigger cell death.

Clinical significance

Mutations in the AAAS gene are responsible for Triple A syndrome (also known as Allgrove Syndrome).^[5] Triple-A syndrome is an autosomal recessive neuroendocrinological disease.

Aladin is also employed in specific oocyte meiotic stages, including spindle assembly and spindle positioning.^[6] Female mice homozygously null for aladin are sterile.

References

Further reading

• Jühlen R, Idkowiak J, Taylor AE, Kind B, Arlt W, Huebner A, Koehler K . Role of ALADIN in human adrenocortical cells for oxidative stress response and steroidogenesis . PLOS ONE . 10 . 4 . e0124582 . 2015 . 25867024 . 10.1371/journal.pone.0124582 . 4395102. 2015PLoSO..1024582J . free .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . January 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Weber A, Wienker TF, Jung M, Easton D, Dean HJ, Heinrichs C, Reis A, Clark AJ . Linkage of the gene for the triple A syndrome to chromosome 12q13 near the type II keratin gene cluster . Human Molecular Genetics . 5 . 12 . 2061–6 . December 1996 . 8968764 . 10.1093/hmg/5.12.2061 . free . 10.1.1.329.7433 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Handschug K, Sperling S, Yoon SJ, Hennig S, Clark AJ, Huebner A . Triple A syndrome is caused by mutations in AAAS, a new WD-repeat protein gene . Human Molecular Genetics . 10 . 3 . 283–90 . February 2001 . 11159947 . 10.1093/hmg/10.3.283 . free .
• Sandrini F, Farmakidis C, Kirschner LS, Wu SM, Tullio-Pelet A, Lyonnet S, Metzger DL, Bourdony CJ, Tiosano D, Chan WY, Stratakis CA . Spectrum of mutations of the AAAS gene in Allgrove syndrome: lack of mutations in six kindreds with isolated resistance to corticotropin . The Journal of Clinical Endocrinology and Metabolism . 86 . 11 . 5433–7 . November 2001 . 11701718 . 10.1210/jcem.86.11.8037 . free .
• Schmittmann-Ohters K, Huebner A, Richter-Unruh A, Hauffa BP . Clinical and novel molecular findings in a 6.8-year-old Turkish boy with triple A syndrome . Hormone Research . 56 . 1–2 . 67–72 . 2002 . 11815731 . 10.1159/000048093 . 46834548 .
• Goizet C, Catargi B, Tison F, Tullio-Pelet A, Hadj-Rabia S, Pujol F, Lagueny A, Lyonnet S, Lacombe D . Progressive bulbospinal amyotrophy in triple A syndrome with AAAS gene mutation . Neurology . 58 . 6 . 962–5 . March 2002 . 11914417 . 10.1212/wnl.58.6.962 .
• Cronshaw JM, Matunis MJ . The nuclear pore complex protein ALADIN is mislocalized in triple A syndrome . Proceedings of the National Academy of Sciences of the United States of America . 100 . 10 . 5823–7 . May 2003 . 12730363 . 156285 . 10.1073/pnas.1031047100 . 2003PNAS..100.5823C . free .
• Prpic I, Huebner A, Persic M, Handschug K, Pavletic M . Triple A syndrome: genotype-phenotype assessment . Clinical Genetics . 63 . 5 . 415–7 . May 2003 . 12752575 . 10.1034/j.1399-0004.2003.00070.x . 19250948 . free .
• Roubergue A, Apartis E, Vidailhet M, Mignot C, Tullio-Pelet A, Lyonnet S, de Villemeur TB . Myoclonus and generalized digestive dysmotility in triple A syndrome with AAAS gene mutation . Movement Disorders . 19 . 3 . 344–6 . March 2004 . 15022193 . 10.1002/mds.10660 . 27038247 .
• Brooks BP, Kleta R, Caruso RC, Stuart C, Ludlow J, Stratakis CA . Triple-A syndrome with prominent ophthalmic features and a novel mutation in the AAAS gene: a case report . BMC Ophthalmology . 4 . 7 . June 2004 . 15217518 . 10.1186/1471-2415-4-7 . 459227 . free .
• Huebner A, Kaindl AM, Knobeloch KP, Petzold H, Mann P, Koehler K . The triple A syndrome is due to mutations in ALADIN, a novel member of the nuclear pore complex . Endocrine Research . 30 . 4 . 891–9 . November 2004 . 15666842 . 10.1081/ERC-200044138 . 31047487 .
• Storr HL, Clark AJ, Priestley JV, Michael GJ . Identification of the sites of expression of triple A syndrome mRNA in the rat using in situ hybridisation . Neuroscience . 131 . 1 . 113–23 . 2005 . 15680696 . 10.1016/j.neuroscience.2004.10.029 . 7323257 .
• Di Nardo G, Tullio-Pelet A, Annese V, Stanghellini V, Barbara G, Latiano A, Andriulli A, Cremon C, Salvioli B, Volta U, Corinaldesi R, Lyonnet S, De Giorgio R . Idiopathic achalasia is not allelic to alacrima achalasia adrenal insufficiency syndrome at the ALADIN locus . Digestive and Liver Disease . 37 . 5 . 312–5 . May 2005 . 15843079 . 10.1016/j.dld.2004.11.006 .
• Li X, Ji C, Gu J, Xu J, Jin Z, Sun L, Zou X, Lin Y, Sun R, Wang P, Gu S, Mao Y . Molecular cloning and characterization of AAAS-V2, a novel splice variant of human AAAS . Molecular Biology Reports . 32 . 2 . 127–31 . June 2005 . 16022285 . 10.1007/s11033-004-6939-9 . 9034337 .
• Brooks BP, Kleta R, Stuart C, Tuchman M, Jeong A, Stergiopoulos SG, Bei T, Bjornson B, Russell L, Chanoine JP, Tsagarakis S, Kalsner L, Stratakis C . Genotypic heterogeneity and clinical phenotype in triple A syndrome: a review of the NIH experience 2000-2005 . Clinical Genetics . 68 . 3 . 215–21 . September 2005 . 16098009 . 10.1111/j.1399-0004.2005.00482.x . 20404052 .
• Papageorgiou L, Mimidis K, Katsani KR, Fakis G . The genetic basis of triple A (Allgrove) syndrome in a Greek family . Gene . 512 . 2 . 505–9 . January 2013 . 23073554 . 10.1016/j.gene.2012.10.008 .

Notes and References

1. Tullio-Pelet A, Salomon R, Hadj-Rabia S, Mugnier C, de Laet MH, Chaouachi B, Bakiri F, Brottier P, Cattolico L, Penet C, Bégeot M, Naville D, Nicolino M, Chaussain JL, Weissenbach J, Munnich A, Lyonnet S . Mutant WD-repeat protein in triple-A syndrome . Nature Genetics . 26 . 3 . 332–5 . November 2000 . 11062474 . 10.1038/81642 . 22952012 .
2. Kind B, Koehler K, Lorenz M, Huebner A . The nuclear pore complex protein ALADIN is anchored via NDC1 but not via POM121 and GP210 in the nuclear envelope . Biochemical and Biophysical Research Communications . 390 . 2 . 205–10 . December 2009 . 19782045 . 10.1016/j.bbrc.2009.09.080 .
3. Cho AR, Yang KJ, Bae Y, Bahk YY, Kim E, Lee H, Kim JK, Park W, Rhim H, Choi SY, Imanaka T, Moon S, Yoon J, Yoon SK . Tissue-specific expression and subcellular localization of ALADIN, the absence of which causes human triple A syndrome . Experimental & Molecular Medicine . 41 . 6 . 381–6 . June 2009 . 19322026 . 2705858 . 10.3858/emm.2009.41.6.043 .
4. Hirano M, Furiya Y, Asai H, Yasui A, Ueno S . ALADINI482S causes selective failure of nuclear protein import and hypersensitivity to oxidative stress in triple A syndrome . Proc. Natl. Acad. Sci. U.S.A. . 103 . 7 . 2298–303 . February 2006 . 16467144 . 1413683 . 10.1073/pnas.0505598103 . 2006PNAS..103.2298H . free .
5. Web site: Entrez Gene: AAAS achalasia, adrenocortical insufficiency, alacrimia (Allgrove, triple-A).
6. Carvalhal S, Stevense M, Koehler K, Naumann R, Huebner A, Jessberger R, Griffis ER . ALADIN is required for the production of fertile mouse oocytes . Mol. Biol. Cell . 28 . 19 . 2470–2478 . September 2017 . 28768824 . 5597320 . 10.1091/mbc.E16-03-0158 .