DNAH11 and common names
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Dynein axonemal heavy chain 11 (DNAH11) is a protein that is encoded by the DNAH11 gene in humans.[5][6] In mice, the protein is encoded by the Dnahc11 gene, the murine homolog to human DNAH11.[7] The protein was previously known as 'left-right' dynein (with the corresponding gene alias lrd) in mice and is particularly notable during embryogenesis for orientation of the eventual body plan.[8][9]
Function
editThis gene encodes a member of the dynein heavy chain family, DNAH11, a microtubule-dependent motor ATPase protein critical for processes involving ciliary movement. The gene DNAH11 has reported associations in a number of important physiological processes including the movement of respiratory cilia, sperm motility, and establishment of the adult body plan.[7][10][11][12] A knockout model of this gene has not been reported.
Embryogenesis
editThe body plan is naturally asymmetrical, and the overall order is defined during embryonic gastrulation in mammals where the three germ layers (endoderm, mesoderm, and ectoderm) are established. At the beginnings of gastrulation, the primitive node serves as the organizer and has motile cilia on its surface.[13][14] These cilia are responsible for directing increased amounts of nodal to the left side of the developing embryo, establishing asymmetry.[7] For this reason, proper expression of DNAH11 is critical for correct establishment and subsequent development of the asymmetrical body plan.
Conditions Associated with DNAH11
editMutations in this DNAH11 have been implicated in causing Primary Ciliary Dyskinesia (PCD), formerly called 'immotile cilia syndrome', and results from abnormally motile or static cilia within the respiratory tract.[7] PCD is characterized by bronchiectasis, frequent upper respiratory tract infections, and issues with fertility, and PCD individuals have increased rates of heterotaxy and situs inversus in approximately 50% of reported cases, a congenital condition in which some organs are mirrored to an abnormal side of the body cavity.[15][16] Mutations in DNAH11 are also associated with Kartagener syndrome (PCD with situs inversus totalis, a congenital condition with a characteristic total inversion of the body plan and organs).[15]
Fertility-Related Effects
editGenetic errors with DNAH11 have been shown to cause a number of fertility-related effects in both sexes. Decreased motile cilia-specific expression of DNAH11 within the axoneme of sperm is associated with lower levels of sperm motility.[17][18] For this reason, males with PCD are not sterile, but they are often infertile under conventional methods due to lack of sperm motility;[6][18] however, there are cases of DNAH11 mutant males fathering offspring without intervention of assisted reproductive technologies.[19][20] In females with PCD or Kartagener's syndrome, there are increased reports of subfertility and risk of ectopic pregnancy.[21][22] Because females' fallopian tubes are lined with motile cilia which show identical motor protein composition to those observed in the respiratory tract, this is believed to result in the increased risks observed in case studies (although affected PCD females' cilia have not been directly analyzed so this remains inconclusive).[23]
References
edit- ^ a b c GRCh38: Ensembl release 89: ENSG00000105877 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000018581 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Chapelin C, Duriez B, Magnino F, Goossens M, Escudier E, Amselem S (Sep 1997). "Isolation of several human axonemal dynein heavy chain genes: genomic structure of the catalytic site, phylogenetic analysis and chromosomal assignment". FEBS Lett. 412 (2): 325–30. doi:10.1016/S0014-5793(97)00800-4. PMID 9256245. S2CID 23935907.
- ^ a b "Entrez Gene: DNAH11 dynein, axonemal, heavy chain 11".
- ^ a b c d Lucas, J. S., Adam, E. C., Goggin, P. M., Jackson, C. L., Powles‐Glover, N., Patel, S. H., ... & Lackie, P. M. (2012). Static respiratory cilia associated with mutations in Dnahc11/DNAH11: a mouse model of PCD. Human mutation, 33(3), 495-503. https://doi.org/10.1002/humu.22001
- ^ Supp, D. M., Brueckner, M., Kuehn, M. R., Witte, D. P., Lowe, L. A., McGrath, J., ... & Potter, S. S. (1999). Targeted deletion of the ATP binding domain of left-right dynein confirms its role in specifying development of left-right asymmetries. Development, 126(23), 5495-5504. https://doi.org/10.1242/dev.126.23.5495
- ^ Xia, H., Huang, X., Deng, S., Xu, H., Yang, Y., Liu, X., ... & Deng, H. (2021). DNAH11 compound heterozygous variants cause heterotaxy and congenital heart disease. PLoS One, 16(6), e0252786. https://doi.org/10.1371/journal.pone.0252786
- ^ Zhu D, Zhang H, Wang R, Liu X, Jiang Y, Feng T, Liu R, Zhang G (June 2019). "Association of DNAH11 gene polymorphisms with asthenozoospermia in Northeast Chinese patients". Bioscience Reports. 39 (6). doi:10.1042/bsr20181450. ISSN 0144-8463. PMC 6617048. PMID 31160482.
- ^ Zariwala MA, Knowles MR, Omran H (2007-03-01). "Genetic Defects in Ciliary Structure and Function". Annual Review of Physiology. 69 (1): 423–450. doi:10.1146/annurev.physiol.69.040705.141301. ISSN 0066-4278. PMID 17059358.
- ^ Wagner MK, Yost HJ (2000-02-15). "Left–right development: The roles of nodal cilia". Current Biology. 10 (4): R149–R151. Bibcode:2000CBio...10.R149W. doi:10.1016/S0960-9822(00)00328-6. ISSN 0960-9822. PMID 10704402.
- ^ Harvey RP (1998-08-07). "Links in the Left/Right Axial Pathway". Cell. 94 (3): 273–276. doi:10.1016/S0092-8674(00)81468-3. ISSN 0092-8674. PMID 9708727.
- ^ Grabowski CT (August 1962). "Neural induction and notochord formation by mesoderm from the node area of the early chick blastoderm". Journal of Experimental Zoology. 150 (3): 233–245. Bibcode:1962JEZ...150..233G. doi:10.1002/jez.1401500307. ISSN 0022-104X. PMID 13949682.
- ^ a b Bartoloni L, Blouin JL, Pan Y, Gehrig C, Maiti AK, Scamuffa N, Rossier C, Jorissen M, Armengot M, Meeks M, Mitchison HM, Chung EM, Delozier-Blanchet CD, Craigen WJ, Antonarakis SE (2002-08-06). "Mutations in the DNAH11 (axonemal heavy chain dynein type 11) gene cause one form of situs inversus totalis and most likely primary ciliary dyskinesia". Proceedings of the National Academy of Sciences. 99 (16): 10282–10286. Bibcode:2002PNAS...9910282B. doi:10.1073/pnas.152337699. ISSN 0027-8424. PMC 124905. PMID 12142464.
- ^ Russakoff AH, Katz HW (1946-08-22). "Dextrocardia and Bronchiectasis: A Review of the Literature and a Report of Two Cases". New England Journal of Medicine. 235 (8): 253–255. doi:10.1056/NEJM194608222350803. ISSN 0028-4793. PMID 20996259.
- ^ Whitfield M, Thomas L, Bequignon E, Schmitt A, Stouvenel L, Montantin G, Tissier S, Duquesnoy P, Copin B, Chantot S, Dastot F, Faucon C, Barbotin AL, Loyens A, Siffroi JP (2019-07-03). "Mutations in DNAH17, Encoding a Sperm-Specific Axonemal Outer Dynein Arm Heavy Chain, Cause Isolated Male Infertility Due to Asthenozoospermia". The American Journal of Human Genetics. 105 (1): 198–212. doi:10.1016/j.ajhg.2019.04.015. ISSN 0002-9297. PMC 6612517. PMID 31178125.
- ^ a b Sironen A, Shoemark A, Patel M, Loebinger MR, Mitchison HM (2019-11-28). "Sperm defects in primary ciliary dyskinesia and related causes of male infertility". Cellular and Molecular Life Sciences. 77 (11): 2029–2048. doi:10.1007/s00018-019-03389-7. ISSN 1420-682X. PMC 7256033. PMID 31781811.
- ^ Vanaken GJ, Bassinet L, Boon M, Mani R, Honoré I, Papon JF, Cuppens H, Jaspers M, Lorent N, Coste A, Escudier E, Amselem S, Maitre B, Legendre M, Christin-Maitre S (2017-11-01). "Infertility in an adult cohort with primary ciliary dyskinesia: phenotype–gene association". European Respiratory Journal. 50 (5). doi:10.1183/13993003.00314-2017. ISSN 0903-1936. PMID 29122913.
- ^ Schwabe GC, Hoffmann K, Loges NT, Birker D, Rossier C, de Santi MM, Olbrich H, Fliegauf M, Failly M, Liebers U, Collura M, Gaedicke G, Mundlos S, Wahn U, Blouin JL (February 2008). "Primary ciliary dyskinesia associated with normal axoneme ultrastructure is caused byDNAH11mutations". Human Mutation. 29 (2): 289–298. doi:10.1002/humu.20656. ISSN 1059-7794. PMID 18022865. S2CID 22292489.
- ^ Blyth M, Wellesley D (April 2008). "Ectopic pregnancy in primary ciliary dyskinesia". J Obstet Gynaecol. 28 (3): 358. doi:10.1080/01443610802058742. PMID 18569496. S2CID 19624982.
- ^ Halbert SA, Patton DL, Zarutskie PW, Soules MR (1997-01-01). "Function and structure of cilia in the fallopian tube of an infertile woman with Kartagener's syndrome". Human Reproduction. 12 (1): 55–58. doi:10.1093/humrep/12.1.55. ISSN 0268-1161. PMID 9043902.
- ^ Raidt J, Werner C, Menchen T, Dougherty GW, Olbrich H, Loges NT, Schmitz R, Pennekamp P, Omran H (2015-09-15). "Ciliary function and motor protein composition of human fallopian tubes". Human Reproduction. 30 (12): 2871–2880. doi:10.1093/humrep/dev227. ISSN 1460-2350. PMID 26373788.
Further reading
edit- Schwabe GC, Hoffmann K, Loges NT, et al. (2008). "Primary ciliary dyskinesia associated with normal axoneme ultrastructure is caused by DNAH11 mutations". Hum. Mutat. 29 (2): 289–98. doi:10.1002/humu.20656. PMID 18022865. S2CID 22292489.
- Cheung PY, Zhang Y, Long J, et al. (2004). "p150(Glued), Dynein, and microtubules are specifically required for activation of MKK3/6 and p38 MAPKs". J. Biol. Chem. 279 (44): 45308–11. doi:10.1074/jbc.C400333200. PMID 15375157.
- Varadi A, Johnson-Cadwell LI, Cirulli V, et al. (2005). "Cytoplasmic dynein regulates the subcellular distribution of mitochondria by controlling the recruitment of the fission factor dynamin-related protein-1". J. Cell Sci. 117 (Pt 19): 4389–400. doi:10.1242/jcs.01299. PMID 15304525.
- Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
- Hillier LW, Fulton RS, Fulton LA, et al. (2003). "The DNA sequence of human chromosome 7". Nature. 424 (6945): 157–64. Bibcode:2003Natur.424..157H. doi:10.1038/nature01782. PMID 12853948.
- Bartoloni L, Blouin JL, Pan Y, et al. (2002). "Mutations in the DNAH11 (axonemal heavy chain dynein type 11) gene cause one form of situs inversus totalis and most likely primary ciliary dyskinesia". Proc. Natl. Acad. Sci. U.S.A. 99 (16): 10282–6. Bibcode:2002PNAS...9910282B. doi:10.1073/pnas.152337699. PMC 124905. PMID 12142464.
- Dias Neto E, Correa RG, Verjovski-Almeida S, et al. (2000). "Shotgun sequencing of the human transcriptome with ORF expressed sequence tags". Proc. Natl. Acad. Sci. U.S.A. 97 (7): 3491–6. Bibcode:2000PNAS...97.3491D. doi:10.1073/pnas.97.7.3491. PMC 16267. PMID 10737800.
- Kastury K, Taylor WE, Gutierrez M, et al. (1997). "Chromosomal mapping of two members of the human dynein gene family to chromosome regions 7p15 and 11q13 near the deafness loci DFNA 5 and DFNA 11". Genomics. 44 (3): 362–4. doi:10.1006/geno.1997.4903. PMID 9325061.