Conservation of anatomically restricted glycosaminoglycan structures in divergent nematode species
Year: 2016
Type: article
Abstract: Heparan sulfates (HS) are glycosaminoglycans of the extracellular matrices and characterized by complex modification patterns owing to sulfations, epimerization, and acetylation. Distinct HS modification patterns have been shown to modulate protein-protein interactions during development in general and of the nervous system in particular. This has led to the heparan sulfate code hypothesis, which posits that specifically modified HS epitopes are distributed in a tissue and cell-specific fashion to orchestrate neural circuit formation. Whether an HS code exists in vivo, how specific or how evolutionarily conserved the anatomical distribution of an HS code may be has remained unknown. Here we conduct a systematic comparison of HS modification patterns in the nematode Caenorhabditis elegans using transgenic expression of 33 different HS-specific single chain variable fragment antibodies. We find that some HS modification patterns are widely distributed in the nervous system. In contrast, other HS modification patterns appear highly cell-specific in both non-neuronal and neuronal cells. Some patterns can be as restricted in their localization as to single neurites or synaptic connections between two neurons. This restricted anatomical localization of specific HS patterns can be evolutionarily conserved over a span of 80-100 million years in the divergent nematode species Caenorhabditis briggsae suggesting structural and, possibly functional conservation of glycosaminoglycan structures similar to proteins. These findings suggest a HS code with subcellularly localized, unique glycan identities in the nervous system.
Source: Glycobiology
Institution: Albert Einstein College of Medicine
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
Funders: Alfred P. Sloan Foundation, National Institutes of Health, Albert Einstein College of Medicine, Yeshiva University, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: In vivo analysis of the HS code, Genetic Analyses of Heparan Sulfate Function in Cell-Cell Interactions, Novel Approaches to Structure/Function Analyses of Heparan Sulfate in vivo, TUSM/T-NEMC CENTER FOR NEUROSCIENCE RESEARCH, G623898943, Training Program in Cellular and Molecular Biology and Genetics, Support for the Rose F. Kennedy IDD Research Center, Cancer Center Support Grant
OpenAlex ID: W2305208944