Heparan Sulfate Heterogeneity in Skeletal Muscle Basal Lamina: Demonstration by Phage Display-Derived Antibodies

Jenniskens, Guido J.; Oosterhof, Arie; Brandwijk, Ricardo; Veerkamp, J.H.; Kuppevelt, Toin H. Van

doi:10.1523/jneurosci.20-11-04099.2000

Cited by 96 publications

(107 citation statements)

References 55 publications

Supporting

Mentioning

103

Contrasting

Order By: Relevance

“…This library contains 10 8 different clones with 50 different V H genes with synthetic random complementarity-determining region 3 regions and one V L gene. The selection of phages displaying scFv antibodies was performed as described (7)(8)(9). The scFv antibodies expressed contain a c-myc tag for detection.…”

Section: Materials-mentioning

confidence: 99%

See 1 more Smart Citation

Detection of 2-O-Sulfated Iduronate and N-Acetylglucosamine Units in Heparan Sulfate by an Antibody Selected against Acharan Sulfate (IdoA2S-GlcNAc)

Dam¹,

Westerlo²,

Smetsers³

et al. 2004

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

The snail glycosaminoglycan acharan sulfate (AS) is structurally related to heparan sulfates (HS) and has a repeating disaccharide structure of ␣-D-N-acetylglucosaminyl-2-O-sulfo-␣-L-iduronic acid (GlcNAc-IdoA2S) residues. Using the phage display technology, a unique antibody (MW3G3) was selected against AS with a V H 3, DP 47, and a CDR3 amino acid sequence of QKKRPRF. Antibody MW3G3 did not react with desulfated, N-deacetylated or N-sulfated AS, indicating that reactivity depends on N-acetyl and 2-O-sulfate groups. Antibody MW3G3 also had a high preference for (modified) heparin oligosaccharides containing N-acetylated glucosamine and 2-O-sulfated iduronic acid residues. In tissues, antibody MW3G3 identified a HS oligosaccharide epitope containing N-acetylated glucosamine and 2-O-sulfated iduronic acid residues as enzymatic N-deacetylation of HS in situ prevented staining, and 2-O-sulfotransferase-deficient Chinese hamster ovary cells were not reactive. An immunohistochemical survey using various rat organs revealed a distinct distribution of the MW3G3 epitope, which was primarily present in the basal laminae of most (but not all) blood vessels and of some epithelia, including human skin. No staining was observed in the glycosaminoglycan-rich tumor matrix of metastatic melanoma. In conclusion, we have selected an antibody that identifies HS oligosaccharides containing N-acetylated glucosamine and 2-O-sulfated iduronic acid residues. This antibody may be instrumental in identifying structural alterations in HS in health and disease.Acharan sulfate (AS) 1 is a glycosaminoglycan (GAG) abundantly present in the giant African snail Achatina fulica (1). It largely consists of the repeating disaccacharide structure of 34)-␣-D-2-acetamido-2-deoxyglucopyranose(134)-␣-L-idopyranosyluronic acid-2-sulfate(13 and is closely related to heparan sulfates. AS is located in large granules present in the outer surface of the snail and is secreted onto the surface as mucus. This mucus consists of 26% proteins, and the GAG moiety is entirely formed by AS. Whether AS is present as a proteoglycan is unclear (2). The pattern of adjacent N-acetylglucosamine and 2-sulfoiduronic acid residues is unusual and suggests interesting biological activities. Among the proposed biological functions of AS in snails are binding, uptake, and transport of divalent cations and functioning as an antidesiccant (1). AS inhibits the mitogenic activity induced by basic fibroblast growth factor (3), angiogenesis (4), and tumor growth (5).To study the cell biological importance of specific HS epitopes and their location in tissue, single chain antibodies have been generated as described by our group (6 -9). These antibodies were selected against HS from various sources and stained differentially in tissues sections from various organs. Defined HS oligosaccharides were used to reveal details of the epitopes recognized by the antibodies (6). Although some chemical groups in HS essential for antibody reactivity could be determined, the oligosaccharide sequence...

show abstract

Section: Materials-mentioning

confidence: 99%

“…Large Scale Preparation of Antibodies-To produce scFv antibodies, periplasmic fractions of infected bacteria were isolated as described (7)(8)(9)20). Bacteria (expressing anti-AS scFv antibodies) were grown and induced by isopropyl-␤-D-thiogalactopyranoside to produce antibodies.…”

Section: Materials-mentioning

confidence: 99%

Detection of 2-O-Sulfated Iduronate and N-Acetylglucosamine Units in Heparan Sulfate by an Antibody Selected against Acharan Sulfate (IdoA2S-GlcNAc)

Dam¹,

Westerlo²,

Smetsers³

et al. 2004

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…This biphasic character of myotube development is thought to be caused by the necessity of primary myotubes to first reach a certain stage of maturation, including sarcolemmal changes, before secondary myotube development can be supported (Ontell and Kozeka, 1984;Jansen and Fladby, 1990). Extracellular (Jenniskens et al, 2000;Dennissen et al, 2002). c Preferred sequence is not known, N-sulfation is indispensible, 6-O sulfation is likely to be inhibitory.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, we reported on the selection of a panel of phage display-derived antibodies that recognize specific HS epitopes (Jenniskens et al, 2000). In the present study, we describe the spatiotemporal distribution of several HS epitopes during myogenesis in mouse intercostal muscle, and their distribution with regard to developing synapses.…”

Section: Introductionmentioning

confidence: 87%

See 1 more Smart Citation

Spatiotemporal distribution of heparan sulfate epitopes during myogenesis and synaptogenesis: A study in developing mouse intercostal muscle

Jenniskens¹,

Hafmans²,

Veerkamp³

et al. 2002

Developmental Dynamics

Self Cite

View full text Add to dashboard Cite

Formation of a basal lamina (BL) ensheathing developing skeletal muscle cells is one of the earliest events in mammalian skeletal muscle myogenesis. BL-resident heparan sulfate proteoglycans have been implicated in various processes during myogenesis, including synaptic differentiation. However, attention has focused on the proteoglycan protein core, ignoring the glycosaminoglycan moiety mainly because of a lack of appropriate tools. Recently, we selected a panel of anti-heparan sulfate antibodies applied here to study the spatiotemporal distribution of specific heparan sulfate (HS) epitopes during myogenesis. In mouse intercostal muscle at embryonic day (E14), formation of acetylcholine receptor clusters at synaptic sites coincides with HS deposition. Although some HS epitopes show a general appearance throughout the BL, one epitope preferably clusters at synaptic sites but does so only from E16 onward. During elongation and maturation of primary myotubes, a process preceding secondary myotube development, significant changes in the HS epitope constitution of both synaptic and extrasynaptic BL were observed. As a whole, the data presented here strengthen previous observations on developmental regulation by BL components, and add to the putative roles of specific HS epitopes in myogenesis and synaptogenesis.

show abstract

Glycosylated synaptomatrix regulation of trans‐synaptic signaling

Dani

Broadie

2011

Developmental Neurobiology

View full text Add to dashboard Cite

Synapse formation is driven by precisely orchestrated intercellular communication between the presynaptic and the postsynaptic cell, involving a cascade of anterograde and retrograde signals. At the neuromuscular junction (NMJ), both neuron and muscle secrete signals into the heavily glycosylated synaptic cleft matrix sandwiched between the two synapsing cells. These signals must necessarily traverse and interact with the extracellular environment, for the ligand-receptor interactions mediating communication to occur. This complex synaptomatrix, rich in glycoproteins and proteoglycans, comprises heterogeneous, compartmentalized domains where specialized glycans modulate trans-synaptic signaling during synaptogenesis and subsequent synapse modulation. The general importance of glycans during development, homeostasis and disease is well established, but this important molecular class has received less study in the nervous system. Glycan modifications are now understood to play functional and modulatory roles as ligands and co-receptors in numerous model systems; however roles in synapse formation and modulation are less well understood. We highlight here properties of synaptomatrix glycans and glycan-interacting proteins with key roles in synaptogenesis, with a particular focus on recent advances made in the Drosophila NMJ genetic system. We discuss open questions and interesting new findings driving the current investigations of the complex, diverse and largely understudied glycan mechanisms. Keywords: Extracellular Matrix, Glycan, Synaptic Cleft, Neuromuscular Junction, Drosophila

show abstract

Heparan Sulfate Heterogeneity in Skeletal Muscle Basal Lamina: Demonstration by Phage Display-Derived Antibodies

Cited by 96 publications

References 55 publications

Detection of 2-O-Sulfated Iduronate and N-Acetylglucosamine Units in Heparan Sulfate by an Antibody Selected against Acharan Sulfate (IdoA2S-GlcNAc)

Detection of 2-O-Sulfated Iduronate and N-Acetylglucosamine Units in Heparan Sulfate by an Antibody Selected against Acharan Sulfate (IdoA2S-GlcNAc)

Spatiotemporal distribution of heparan sulfate epitopes during myogenesis and synaptogenesis: A study in developing mouse intercostal muscle

Glycosylated synaptomatrix regulation of trans‐synaptic signaling

Contact Info

Product

Resources

About