Influencing Early Stages of Neuromuscular Junction Formation through Glycocalyx Engineering
Year: 2018
Type: article
Abstract: Achieving molecular control over the formation of synaptic contacts in the nervous system can provide important insights into their regulation and can offer means for creating well-defined in vitro systems to evaluate modes of therapeutic intervention. Agrin-induced clustering of acetylcholine receptors (AChRs) at postsynaptic sites is a hallmark of the formation of the neuromuscular junction, a synapse between motoneurons and muscle cells. In addition to the cognate agrin receptor LRP4 (low-density lipoprotein receptor related protein-4), muscle cell heparan sulfate (HS) glycosaminoglycans (GAGs) have also been proposed to contribute to AChR clustering by acting as agrin co-receptors. Here, we provide direct evidence for the role of HS GAGs in agrin recruitment to the surface of myotubes, as well as their functional contributions toward AChR clustering. We also demonstrate that engineering of the myotube glycocalyx using synthetic HS GAG polymers can replace native HS structures to gain control over agrin-mediated AChR clustering.
Source: ACS Chemical Neuroscience
Institution: University of California San Diego
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: Alfred P. Sloan Foundation, Research Corporation for Science Advancement, National Institutes of Health, University of California, San Diego, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences, National Institute of Child Health and Human Development, Division of Graduate Education, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Chemical editing of nanoscale proteoglycan architecture and organization to control cellular differentiation, Chemical editing of nanoscale proteoglycan architecture and organization to control cellular, Chemical Biology Interfaces at UC San Diego, G1912873702, Glycan Modulation of Inflammatory Responses, In vivo glycan engineering at the cell-matrix interface to control stem cell fate
OpenAlex ID: W2887381055