Transitional Expression of Neural Cell Adhesion Molecule Isoforms During Chicken Embryonic Myogenesis.

Yoshimi, Tatsuya; Mimura, Naotoshi; Aimoto, Saburo; Asano, Atsushi

doi:10.1247/csf.18.1

Cited by 10 publications

(17 citation statements)

References 31 publications

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“…Thus, each splice variant of NCAM that differs in its attachment to the plasma membrane can also be expressed either containing or lacking the MSD region. This interpretation of the identity of NCAM polypeptides is in agreement with the studies of Yoshimi et al (1993) on the 155-and 145-kD forms of NCAM expressed during skeletal muscle development.…”

Section: Discussionsupporting

confidence: 90%

NCAM polypeptides in heart development: association with Z discs of forms that contain the muscle-specific domain.

Byeon

Sugi

Markwald

et al. 1995

The Journal of Cell Biology

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Abstract. Previous studies of neural cell adhesion molecule (NCAM) cDNAs have revealed an alternatively spliced set of small exons (12A, 12B, 12C, and 12D) that encode a region in the extracellular portion of the molecule known as the muscle-specific domain (MSD). The entire MSD region can be expressed in skeletal muscle, heart, and skin; only exons 12A and 12D have been found in brain. These studies did not reveal which NCAM polypeptides contain the MSD region or the immunohistochemical distribution of these NCAM molecules. To address these questions, we prepared antibodies against the oligopeptides encoded by exons 12A and 12B and by exons 12C and 12D, and we used these antibodies to study the forms of NCAM containing the MSD region expressed during embryonic chicken heart development. These antibodies recognize certain forms of NCAM found in the heart, but they do not recognize brain NCAM. In the heart, each of the splice variants of NCAM (large cytoplasmic domain, small cytoplasmic domain, and small surface domain) that differ in their mode of attachment to the plasma membrane or in the size of their cytoplasmic domain is expressed in a form that contains and in a form that lacks the MSD region. No microheterogeneity is observed in the size of NCAM molecules containing the MSD region, even at the level of cyanogen bromide fragments, suggesting that exons 12A-D are expressed as a single unit. Depending on the site and the stage of development, the percent of NCAM molecules containing the MSD region can vary from nearly 0 to 100%. In general, this percentage increases during development. In immunohistochemical studies of hearts from stage 18 embryos, forms of NCAM containing the MSD region colocalized with Z discs. No other adhesion molecules were found in this distribution at this early stage of development. Studies on isolated cells in vitro demonstrate that the colocalization with Z discs of NCAM molecules containing the MSD region does not depend on cell-cell contact, and they raise the possibility that this form of NCAM is involved in cell-extracellular matrix interactions. The association of NCAM molecules containing the MSD region with Z discs suggests that this form of NCAM is involved in early myofibrillogenesis.

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Section: Discussionsupporting

confidence: 90%

NCAM polypeptides in heart development: association with Z discs of forms that contain the muscle-specific domain.

Byeon

Sugi

Markwald

et al. 1995

The Journal of Cell Biology

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“…As reported by Yoshimi et al (1993) we found the 155-kD isoform to be transiently expressed, being high between St 32-38 and then being down regulated along with the 145-kD isoform later in development. The tightly and differentially regulated expression of all three isoforms during in vivo myogenesis suggests that they may be playing distinct roles.…”

Section: Regulation Of Ncam Isoforms During Primary and Secondary Myosupporting

confidence: 85%

“…Some molecular weight variations in these reported forms could also be due to variations in glycosylation other than sialylation or to differing phosphorylation states (Sorkin et al, 1984;Rutishauser et al, 1988;Hoffman et al, 1982). However Yoshimi et al (1993) have reported that in chick thigh muscle from the same embryonic stages that we have studied, the 155-kD isoform has the muscle-specific domain (MSD) insert , whereas the 145-kD isoform does not. They also reported that the MSD domain is present in the 130-kD isoform.…”

Section: Regulation Of Ncam Isoforms During Primary and Secondary Myomentioning

confidence: 90%

Regulation and activity-dependence of N-cadherin, NCAM isoforms, and polysialic acid on chick myotubes during development.

Fredette

Rutishauser

Landmesser

1993

The Journal of Cell Biology

108

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Abstract. Muscle development in vivo involves a complex sequence of cell-cell interactions in which secondary myotubes first form in association with primary myotubes and subsequently separate from them. We show here that during this process N-cadherin and the different structural forms of NCAM are regulated in a pattern that involves both temporal changes in expression and localization to particular regions of the muscle cell surface. In particular, levels of N-cadherin on maturing myotubes are decreased, and the form of NCAM synthesized by the muscle changes from a transmembrane non-polysialylated to a lipid-linked polysialylated membrane protein. Moreover, while NCAM was distributed on all myotube surfaces, the polysialylated form of NCAM was restricted to regions of the myotube surface that had recently separated from neighboring cells. We previously found that blockade of nerve-induced activity by d-Tubocurarine perturbed muscle cell interactions, resulting in a failure of myotubes to separate. We now show that this activity blockade also alters adhesion molecule expression. First, N-cadherin was no longer down-regulated in maturing myotubes, and its persistence on the surfaces of mature myotubes may partly explain their failure to separate. Secondly, the developmental switch from transmembrane to lipid-linked NCAM did not occur, and polysialylated NCAM was no longer formed. As the unusual physical properties of PSA have been proposed to impede cell-cell interactions, this alteration would also be expected to compromise cell separation. Together, these results suggest that the regulated expression of both N-cadherin and NCAM isoforms including their polysialylation, is an essential mechanism for the normal separation of secondary myotubes from primary myotubes.

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“…2B, second row). The blot of sialidase-treated NCAM shows switching in the synthesis of NCAM from the TM form to the GPI ϩ MSD form as differentiation progresses, consistent with the developmental change of NCAM isoforms in chick embryonic muscle (25). Lectin blots using PNA, which is specific for O-linked Gal␤1-3GalNAc, showed that the GPI ϩ MSD isoform is O-glycosylated during days 2-8 (Fig.…”

Section: Ncam-msd and Polysialic Acid Are Sequentially Expressed On Tsupporting

confidence: 72%

Polysialic Acid and Mucin Type O-Glycans on the Neural Cell Adhesion Molecule Differentially Regulate Myoblast Fusion

Suzuki

Angata

Nakayama

et al. 2003

Journal of Biological Chemistry

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Polysialic acid attached to the neural cell adhesion molecule (NCAM) is thought to play a critical role in development. NCAM in muscle tissue contains a muscle-specific domain (MSD) to which mucin type O-glycans are attached. In the present study, using the C2C12 myoblast system, we show that NCAM containing MSD is increasingly expressed on the cell surface as myotubes form. Polysialic acid is primarily attached to N-glycans of NCAM, and polysialylated NCAM is expressed on the outer surface of myotube bundles. By transfecting cDNAs encoding wild type and mutant forms of NCAM, we found that NCAM containing MSD facilitates myoblast fusion, and this effect is diminished by mutating O-glycosylation sites at MSD. By contrast, forced expression of polysialic acid in early differentiation stages reduces myotube formation and delays the expression of NCAM containing the MSD domain. Strikingly, inhibition of polysialic acid synthesis by antisense DNA approach induced differentiation in both human rhabdomyosarcoma cells, which overexpress polysialic acid, and C2C12 cells. These results indicate that polysialic acid and mucin type O-glycans on NCAM differentially regulate myoblast fusion, playing critical roles in muscle development.During mammalian embryonic development, muscle development is initiated once mesenchymal cells commit to become myoblasts. Myoblasts then align and fuse, forming multinucleated myotubes, and mature myotubes are bundled together, forming sarcolemma. In parallel, each myotube starts contraction, receives innervation from motor and sensory neurons, and eventually forms muscle tissue. In this process, one of the most intriguing steps is myoblast fusion. Myoblast fusion consists of multiple steps: expression of the fusion competent phenotype, specific myoblast-myoblast recognition and alignment, cell adhesion and electrical coupling, and fusion of lipid bilayer membrane (1). It has been reported that anti-NCAM 1 antibody inhibits aggregation of fusion-competent chick embryo myoblasts (2), indicating that cell-cell adhesion via NCAM apparently initiates myoblast fusion. In addition, integrins, N-cadherin, VCAM, and VLA4 are thought to be involved (see Ref. 3 and references herein).NCAM is found in several isoforms due to alternative mRNA splicing of more than 19 exons. In mammalian brain, the glycosylphosphatidylinositol (GPI)-anchored 120-kDa isoform and transmembrane 140-and 180-kDa isoforms are primarily expressed. In muscles, three isoforms have been reported: a GPIanchored 125-kDa isoform and transmembrane 140-and 155-kDa isoforms (4). Muscle-specific domain (MSD) was identified in the cDNA of the 125-kDa NCAM isoform obtained from human skeletal muscle (5). MSD is encoded by four different exons, MSD1a, MSD1b, MSD1c, and codon AAG. The fulllength MSD sequence consists of 35 amino acids inserted between two fibronectin type III domains of NCAM. MSD insertion is observed only in skeletal muscle and heart and not in other tissues. O-Glycosylation of MSD was shown by peanut agglutinin (PNA) lecti...

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Transitional Expression of Neural Cell Adhesion Molecule Isoforms During Chicken Embryonic Myogenesis.

Cited by 10 publications

References 31 publications

NCAM polypeptides in heart development: association with Z discs of forms that contain the muscle-specific domain.

NCAM polypeptides in heart development: association with Z discs of forms that contain the muscle-specific domain.

Regulation and activity-dependence of N-cadherin, NCAM isoforms, and polysialic acid on chick myotubes during development.

Polysialic Acid and Mucin Type O-Glycans on the Neural Cell Adhesion Molecule Differentially Regulate Myoblast Fusion

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