The synaptic CT carbohydrate modulates binding and expression of extracellular matrix proteins in skeletal muscle: Partial dependence on utrophin.

Full Abstract

The CT carbohydrate, Neu5Ac/Neu5Gcalpha2,3[GalNAcbeta1,4]Galbeta1,4GlcNAcbeta-, is specifically expressed at the neuromuscular junction in skeletal myofibers of adult vertebrates. When Galgt2, the glycosyltransferase that creates the synaptic beta1,4GalNAc portion of this glycan, is overexpressed in extrasynaptic regions of the myofiber membrane, alpha dystroglycan becomes glycosylated with the CT carbohydrate and this coincides with the ectopic expression of synaptic dystroglycan-binding proteins, including laminin alpha4, laminin alpha5, and utrophin. Here we show that both synaptic and extrasynaptic forms of laminin and agrin have increased binding to the CT carbohydrate compared to sialyl-N-acetyllactosamine, its extrasynaptically expressed precursor. Muscle laminins also show increased binding to CT-glycosylated muscle alpha dystroglycan relative to its non-CT-containing glycoforms. Overexpression of Galgt2 in transgenic mouse skeletal muscle increased the mRNA expression of extracellular matrix (ECM) genes, including agrin and laminin alpha5, as well as utrophin, integrin alpha7, and neuregulin. Increased expression of ECM proteins in Galgt2 transgenic skeletal muscles was partially dependent on utrophin, but utrophin was not required for Galgt2-induced changes in muscle growth or neuromuscular development. These experiments demonstrate that overexpression of a synaptic carbohydrate can increase both ECM binding to alpha dystroglycan and ECM expression in skeletal muscle, and they suggest a mechanism by which Galgt2 overexpression may inhibit muscular dystrophy and affect neuromuscular development.

Author information

Author/s: Yoon, Jung Hae (JH); Chandrasekharan, Kumaran (K); Xu, Rui (R); Glass, Matthew (M); Singhal, Neha (N); Martin, Paul T (PT);

Affiliation: Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Department of Pediatrics, Ohio State University College of Medicine, 700 Children's Drive, Columbus, OH 43205, USA.

Grants: AR049722 (Agency:NIAMS NIH HHS) ; AR050202 (Agency:NIAMS NIH HHS) ; GM62116 (Agency:NIGMS NIH HHS)

Journal and publication information

Publication Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural

Journal: Molecular and cellular neurosciences (Mol Cell Neurosci), published in United States. (Language: eng)

Reference: 2009-Aug; vol 41 (issue 4) : pp 448-63

Dates: Created 2009/06/22; Completed 2009/09/07; Revised 2009/09/25;

PMID: 19442736, status: MEDLINE (last retrieval date: 9/28/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Agrin - metabolism
Animals
Cell Line, Transformed
Dystroglycans - metabolism
Dystrophin - metabolism
Extracellular Matrix Proteins - metabolism
Gene Expression Regulation - physiology
Glycosyltransferases - genetics; metabolism
Humans

Humans
Lamins - metabolism
Mice
Mice, Transgenic
Muscle, Skeletal - metabolism
Neuromuscular Junction - metabolism
Protein Binding - drug effects; genetics
Transfection - methods
Utrophin - genetics; metabolism

Associated Chemicals: Agrin (0) ; Dystrophin (0) ; Extracellular Matrix Proteins (0) ; Lamins (0) ; Utrophin (0) ; Dystroglycans (146888-27-9) ; Glycosyltransferases (EC 2.4.-) ; Galgt2 protein, mouse (EC 2.4.1.-)

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