Glycosylation defects in muscular dystrophies
- PMID: 15367856
- DOI: 10.1097/00019052-200410000-00002
Glycosylation defects in muscular dystrophies
Abstract
Purpose of review: Congenital disorders of glycosylation are caused by defects in the synthesis of the glycan moiety of glycoproteins or other glycoconjugates. There has been a great explosion in the number of neuromuscular diseases caused by mutations in genes that affect carbohydrate metabolism or protein glycosylation. A common defect in these disorders is the defective processing of alpha-dystroglycan.
Recent findings: Recent advances demonstrating mutations in glycosyltransferases and dysfunction of the alpha-beta dystroglycan axis causing different forms of muscular dystrophy, especially with brain involvement, shows clearly that muscle integrity is dependent on glycosylation. We first review the newly identified muscular dystrophies, with a focus on the hypoglycosylation of alpha-dystroglycan, from a clinical, biochemical and genetic standpoint, and second hereditary inclusion body myopathies caused by mutations in the gene that encodes an enzyme responsible for the protein's posttranslational modification that cause sialidation defects. It is shown very recently that molecular recognition of dystroglycan by LARGE is a key determinant in the biosynthetic pathway to produce mature and functional dystroglycan. Gene transfer of LARGE into the cells of individuals with congenital muscular dystrophies restores alpha-dystroglycan function.
Summary: The clinical spectrum of congenital disorders of glycosylation is becoming increasingly broad. A demonstration of mutations in glycosyltransferases will further help to design diagnostic tools and therapeutic approaches. Recent findings which show that molecular recognition by LARGE is essential for expression of functional dystroglycan and LARGE can functionally bypass alpha-dystroglycan glycosylation defects in distinct congenital muscular dystrophies, indicate a new therapeutic strategy.
Similar articles
-
Aberrant glycosylation of alpha-dystroglycan and congenital muscular dystrophies.Acta Myol. 2005 Oct;24(2):64-9. Acta Myol. 2005. PMID: 16550917 Review.
-
LARGE can functionally bypass alpha-dystroglycan glycosylation defects in distinct congenital muscular dystrophies.Nat Med. 2004 Jul;10(7):696-703. doi: 10.1038/nm1059. Epub 2004 Jun 6. Nat Med. 2004. PMID: 15184894
-
Mutations in the human LARGE gene cause MDC1D, a novel form of congenital muscular dystrophy with severe mental retardation and abnormal glycosylation of alpha-dystroglycan.Hum Mol Genet. 2003 Nov 1;12(21):2853-61. doi: 10.1093/hmg/ddg307. Epub 2003 Sep 9. Hum Mol Genet. 2003. PMID: 12966029
-
Journey into muscular dystrophies caused by abnormal glycosylation.Acta Myol. 2004 Sep;23(2):79-84. Acta Myol. 2004. PMID: 15605948 Review.
-
Mutations in B3GALNT2 cause congenital muscular dystrophy and hypoglycosylation of α-dystroglycan.Am J Hum Genet. 2013 Mar 7;92(3):354-65. doi: 10.1016/j.ajhg.2013.01.016. Epub 2013 Feb 28. Am J Hum Genet. 2013. PMID: 23453667 Free PMC article.
Cited by
-
Lectin binding to pectoral fin of neonate little skates reared under ambient and projected-end-of-century temperature regimes.J Morphol. 2024 May;285(5):e21698. doi: 10.1002/jmor.21698. J Morphol. 2024. PMID: 38669130
-
Remarkable Homeostasis of Protein Sialylation in Skeletal Muscles of Hibernating Daurian Ground Squirrels (Spermophilus dauricus).Front Physiol. 2020 Feb 7;11:37. doi: 10.3389/fphys.2020.00037. eCollection 2020. Front Physiol. 2020. PMID: 32116753 Free PMC article.
-
A recurrent missense variant in SLC9A7 causes nonsyndromic X-linked intellectual disability with alteration of Golgi acidification and aberrant glycosylation.Hum Mol Genet. 2019 Feb 15;28(4):598-614. doi: 10.1093/hmg/ddy371. Hum Mol Genet. 2019. PMID: 30335141 Free PMC article.
-
Biological roles of glycans.Glycobiology. 2017 Jan;27(1):3-49. doi: 10.1093/glycob/cww086. Epub 2016 Aug 24. Glycobiology. 2017. PMID: 27558841 Free PMC article. Review.
-
Dystroglycan does not contribute significantly to kidney development or function, in health or after injury.Am J Physiol Renal Physiol. 2011 Mar;300(3):F811-20. doi: 10.1152/ajprenal.00725.2010. Epub 2011 Jan 5. Am J Physiol Renal Physiol. 2011. PMID: 21209007 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous