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The evolution of the dystroglycan complex, a major mediator of muscle integrity.

Adams JC, Brancaccio A - Biol Open (2015)

Bottom Line: This comprises the non-covalently-associated extracellular α-DG, that interacts with laminin in the BM, and the transmembrane β-DG, that interacts principally with dystrophin to connect to the actin cytoskeleton.Phylogenetic analysis based on the C-terminal IG2_MAT_NU region identified three distinct clades corresponding to deuterostomes, arthropods, and mollusks/early-diverging metazoans.Whereas the glycosyltransferases that modify α-DG are also present in choanoflagellates, the DG-binding proteins dystrophin and laminin originated at the base of the metazoa, and DG-associated sarcoglycan is restricted to cnidarians and bilaterians.

View Article: PubMed Central - PubMed

Affiliation: School of Biochemistry, University of Bristol, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK.

No MeSH data available.


Related in: MedlinePlus

Domain architectures of dystroglycans from different animal phyla. (A) The DG typical of vertebrates Callorhincus milii (elephant shark), Lethenteron japonicum (Cyclostomata), (Strongylocentrotus purpuratus (Echinoderma) and an annelid, Capitella teleta. (B-J) domain architectures of DG identified in (B) Urochordata (Ciona intestinalis) and Cephalochordata (Branchiostoma lanceolatum), (C) Hemichordata (Saccoglossus kowalevskii), (D) Mollusca, (Gastropods Lottia gigantea and Aplysia californica, Bivalve, Crassostrea gigas and cephalopod, Octopus vulgaris), (E) arthropod classes (Insecta and Hymenoptera, Camponotus floridanus and others) (see also supplementary material Fig. S1), (F) Nematoda (Caenorhabditis elegans and Caenorhabditis remanei), (G) Cnidaria, Hydra magnipapillata, (H) Cnidaria, Nematostella vectensis (see also supplementary material Fig. S2), (I) Placozoa (Trichoplax adhaerens), (J) Porifera (homoscleromorph Oscarella carmela) (see also supplementary material Fig. S3). Expansions of the IG2_MAT_NU module are indicated in C, E and I (2×) and in H (6×). Black arrowheads indicate the furin cleavage site. Red arrowheads indicate the Gly-Ser α/β maturation site. SP, signal peptide; IG1 and IG2, immunoglobulin-like domains; S6, S6-like domain; βBS, β-subunit binding site on the IG2 domain; MAT, C-terminal region of α-dystroglycan upstream of the Gly-Ser maturation site; NU, natively unfolded region that forms the N-terminal region of the ectodomain of β-dystroglycan; TM, transmembrane; cyto, cytoplasmic domain; DBS, dystrophin-binding site. The SP is reported as a black box if complete, or a white box if partial. Dotted lines indicate protein sequences that are incomplete at the N-terminal end. Dotted boxes around the IG domains of Urochordata (B) or the S6 domain of nematodes (F) indicate the divergence of these domains (less than 20% sequence identity). The dotted box for NU in H. magnipapillata DG (G) indicates the presence of two deletions in this region. The white box within the cytoplasmic domain of N. vectensis DG (H) indicates the presence of an insertion. In T. adhaerens DG (I), no DBS was detected (white box). Diagrams are not to scale. Accession codes and other details are in Table 2.
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BIO012468F1: Domain architectures of dystroglycans from different animal phyla. (A) The DG typical of vertebrates Callorhincus milii (elephant shark), Lethenteron japonicum (Cyclostomata), (Strongylocentrotus purpuratus (Echinoderma) and an annelid, Capitella teleta. (B-J) domain architectures of DG identified in (B) Urochordata (Ciona intestinalis) and Cephalochordata (Branchiostoma lanceolatum), (C) Hemichordata (Saccoglossus kowalevskii), (D) Mollusca, (Gastropods Lottia gigantea and Aplysia californica, Bivalve, Crassostrea gigas and cephalopod, Octopus vulgaris), (E) arthropod classes (Insecta and Hymenoptera, Camponotus floridanus and others) (see also supplementary material Fig. S1), (F) Nematoda (Caenorhabditis elegans and Caenorhabditis remanei), (G) Cnidaria, Hydra magnipapillata, (H) Cnidaria, Nematostella vectensis (see also supplementary material Fig. S2), (I) Placozoa (Trichoplax adhaerens), (J) Porifera (homoscleromorph Oscarella carmela) (see also supplementary material Fig. S3). Expansions of the IG2_MAT_NU module are indicated in C, E and I (2×) and in H (6×). Black arrowheads indicate the furin cleavage site. Red arrowheads indicate the Gly-Ser α/β maturation site. SP, signal peptide; IG1 and IG2, immunoglobulin-like domains; S6, S6-like domain; βBS, β-subunit binding site on the IG2 domain; MAT, C-terminal region of α-dystroglycan upstream of the Gly-Ser maturation site; NU, natively unfolded region that forms the N-terminal region of the ectodomain of β-dystroglycan; TM, transmembrane; cyto, cytoplasmic domain; DBS, dystrophin-binding site. The SP is reported as a black box if complete, or a white box if partial. Dotted lines indicate protein sequences that are incomplete at the N-terminal end. Dotted boxes around the IG domains of Urochordata (B) or the S6 domain of nematodes (F) indicate the divergence of these domains (less than 20% sequence identity). The dotted box for NU in H. magnipapillata DG (G) indicates the presence of two deletions in this region. The white box within the cytoplasmic domain of N. vectensis DG (H) indicates the presence of an insertion. In T. adhaerens DG (I), no DBS was detected (white box). Diagrams are not to scale. Accession codes and other details are in Table 2.

Mentions: The mature form of DG is a type I transmembrane protein composed of two non-covalently interacting subunits: α-DG, which is extracellular and highly glycosylated, and β-DG, which contains the transmembrane and cytoplasmic domains (Ibraghimov-Beskrovnaya et al., 1992) (Fig. 1A). The two subunits are produced from a single transcript, with α-DG liberated in the endoplasmic reticulum by an unknown enzyme. During trafficking through the Golgi apparatus, crucial glycosyltransferases, SGK196, an O-mannose kinase (Yoshida-Moriguchi et al., 2013), and B4GAT1, a glucuronyltransferase (Praissman et al., 2014; Willer et al., 2014), act in a concerted and chronologically regulated fashion to modify the α-DG core protein. These modifications are essential for the downstream enzymatic action of like-acetylglucosaminyltransferase (LARGE), which adds a repeating disaccharide unit [-α3-GlcA-β3-Xyl-] to a mucin-like, central region of α-DG. These carbohydrate decorations of α-DG are important for the calcium-dependent, high-affinity binding of α-DG to the LG4 and LG5 domains of laminin α-subunits (Barresi and Campbell, 2006; Hara et al., 2011a; Tisi et al., 2000; Harrison et al., 2007) as well as to a number of other LG domain-containing extracellular ligands of α-DG, including agrin, perlecan and neurexin (see Sciandra et al., 2013 and references therein). Intracellularly, the extreme C-terminus of β-DG binds to the cysteine-rich, C-terminal domain of the actin-binding protein, dystrophin, ensuring a connection to the F-actin cytoskeleton (Jung et al., 1995). The C-terminus also interacts with the dystrophin-related protein, utrophin, which is predominantly expressed at neuro-muscular junctions (Ishikawa-Sakurai et al., 2004).


The evolution of the dystroglycan complex, a major mediator of muscle integrity.

Adams JC, Brancaccio A - Biol Open (2015)

Domain architectures of dystroglycans from different animal phyla. (A) The DG typical of vertebrates Callorhincus milii (elephant shark), Lethenteron japonicum (Cyclostomata), (Strongylocentrotus purpuratus (Echinoderma) and an annelid, Capitella teleta. (B-J) domain architectures of DG identified in (B) Urochordata (Ciona intestinalis) and Cephalochordata (Branchiostoma lanceolatum), (C) Hemichordata (Saccoglossus kowalevskii), (D) Mollusca, (Gastropods Lottia gigantea and Aplysia californica, Bivalve, Crassostrea gigas and cephalopod, Octopus vulgaris), (E) arthropod classes (Insecta and Hymenoptera, Camponotus floridanus and others) (see also supplementary material Fig. S1), (F) Nematoda (Caenorhabditis elegans and Caenorhabditis remanei), (G) Cnidaria, Hydra magnipapillata, (H) Cnidaria, Nematostella vectensis (see also supplementary material Fig. S2), (I) Placozoa (Trichoplax adhaerens), (J) Porifera (homoscleromorph Oscarella carmela) (see also supplementary material Fig. S3). Expansions of the IG2_MAT_NU module are indicated in C, E and I (2×) and in H (6×). Black arrowheads indicate the furin cleavage site. Red arrowheads indicate the Gly-Ser α/β maturation site. SP, signal peptide; IG1 and IG2, immunoglobulin-like domains; S6, S6-like domain; βBS, β-subunit binding site on the IG2 domain; MAT, C-terminal region of α-dystroglycan upstream of the Gly-Ser maturation site; NU, natively unfolded region that forms the N-terminal region of the ectodomain of β-dystroglycan; TM, transmembrane; cyto, cytoplasmic domain; DBS, dystrophin-binding site. The SP is reported as a black box if complete, or a white box if partial. Dotted lines indicate protein sequences that are incomplete at the N-terminal end. Dotted boxes around the IG domains of Urochordata (B) or the S6 domain of nematodes (F) indicate the divergence of these domains (less than 20% sequence identity). The dotted box for NU in H. magnipapillata DG (G) indicates the presence of two deletions in this region. The white box within the cytoplasmic domain of N. vectensis DG (H) indicates the presence of an insertion. In T. adhaerens DG (I), no DBS was detected (white box). Diagrams are not to scale. Accession codes and other details are in Table 2.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4582122&req=5

BIO012468F1: Domain architectures of dystroglycans from different animal phyla. (A) The DG typical of vertebrates Callorhincus milii (elephant shark), Lethenteron japonicum (Cyclostomata), (Strongylocentrotus purpuratus (Echinoderma) and an annelid, Capitella teleta. (B-J) domain architectures of DG identified in (B) Urochordata (Ciona intestinalis) and Cephalochordata (Branchiostoma lanceolatum), (C) Hemichordata (Saccoglossus kowalevskii), (D) Mollusca, (Gastropods Lottia gigantea and Aplysia californica, Bivalve, Crassostrea gigas and cephalopod, Octopus vulgaris), (E) arthropod classes (Insecta and Hymenoptera, Camponotus floridanus and others) (see also supplementary material Fig. S1), (F) Nematoda (Caenorhabditis elegans and Caenorhabditis remanei), (G) Cnidaria, Hydra magnipapillata, (H) Cnidaria, Nematostella vectensis (see also supplementary material Fig. S2), (I) Placozoa (Trichoplax adhaerens), (J) Porifera (homoscleromorph Oscarella carmela) (see also supplementary material Fig. S3). Expansions of the IG2_MAT_NU module are indicated in C, E and I (2×) and in H (6×). Black arrowheads indicate the furin cleavage site. Red arrowheads indicate the Gly-Ser α/β maturation site. SP, signal peptide; IG1 and IG2, immunoglobulin-like domains; S6, S6-like domain; βBS, β-subunit binding site on the IG2 domain; MAT, C-terminal region of α-dystroglycan upstream of the Gly-Ser maturation site; NU, natively unfolded region that forms the N-terminal region of the ectodomain of β-dystroglycan; TM, transmembrane; cyto, cytoplasmic domain; DBS, dystrophin-binding site. The SP is reported as a black box if complete, or a white box if partial. Dotted lines indicate protein sequences that are incomplete at the N-terminal end. Dotted boxes around the IG domains of Urochordata (B) or the S6 domain of nematodes (F) indicate the divergence of these domains (less than 20% sequence identity). The dotted box for NU in H. magnipapillata DG (G) indicates the presence of two deletions in this region. The white box within the cytoplasmic domain of N. vectensis DG (H) indicates the presence of an insertion. In T. adhaerens DG (I), no DBS was detected (white box). Diagrams are not to scale. Accession codes and other details are in Table 2.
Mentions: The mature form of DG is a type I transmembrane protein composed of two non-covalently interacting subunits: α-DG, which is extracellular and highly glycosylated, and β-DG, which contains the transmembrane and cytoplasmic domains (Ibraghimov-Beskrovnaya et al., 1992) (Fig. 1A). The two subunits are produced from a single transcript, with α-DG liberated in the endoplasmic reticulum by an unknown enzyme. During trafficking through the Golgi apparatus, crucial glycosyltransferases, SGK196, an O-mannose kinase (Yoshida-Moriguchi et al., 2013), and B4GAT1, a glucuronyltransferase (Praissman et al., 2014; Willer et al., 2014), act in a concerted and chronologically regulated fashion to modify the α-DG core protein. These modifications are essential for the downstream enzymatic action of like-acetylglucosaminyltransferase (LARGE), which adds a repeating disaccharide unit [-α3-GlcA-β3-Xyl-] to a mucin-like, central region of α-DG. These carbohydrate decorations of α-DG are important for the calcium-dependent, high-affinity binding of α-DG to the LG4 and LG5 domains of laminin α-subunits (Barresi and Campbell, 2006; Hara et al., 2011a; Tisi et al., 2000; Harrison et al., 2007) as well as to a number of other LG domain-containing extracellular ligands of α-DG, including agrin, perlecan and neurexin (see Sciandra et al., 2013 and references therein). Intracellularly, the extreme C-terminus of β-DG binds to the cysteine-rich, C-terminal domain of the actin-binding protein, dystrophin, ensuring a connection to the F-actin cytoskeleton (Jung et al., 1995). The C-terminus also interacts with the dystrophin-related protein, utrophin, which is predominantly expressed at neuro-muscular junctions (Ishikawa-Sakurai et al., 2004).

Bottom Line: This comprises the non-covalently-associated extracellular α-DG, that interacts with laminin in the BM, and the transmembrane β-DG, that interacts principally with dystrophin to connect to the actin cytoskeleton.Phylogenetic analysis based on the C-terminal IG2_MAT_NU region identified three distinct clades corresponding to deuterostomes, arthropods, and mollusks/early-diverging metazoans.Whereas the glycosyltransferases that modify α-DG are also present in choanoflagellates, the DG-binding proteins dystrophin and laminin originated at the base of the metazoa, and DG-associated sarcoglycan is restricted to cnidarians and bilaterians.

View Article: PubMed Central - PubMed

Affiliation: School of Biochemistry, University of Bristol, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK.

No MeSH data available.


Related in: MedlinePlus