Invited Speaker Abstract 2018 Hunter Cell Biology Meeting

Understanding the cellular glycan surface for central nervous system targeting and imaging (#41)

Lindsay Parker 1 , Arun Everest-Dass 1 2 , Nicole M Cordina 1 , Christopher Ashwood1 1 , Philipp Reineck 3 , Mina Ghanimi-Fard 1 , Nicolle H Packer 1 2
  1. ARC Centre of Excellence for Nanoscale BioPhotonics and Department of Molecular Sciences, Macquarie University, Sydney, NSW, Australia
  2. Institute for Glycomics, Griffith University, Gold Coast, QLD, Australia
  3. ARC Centre of Excellence for Nanoscale BioPhotonics, School of Science, RMIT University, Melbourne, VIC, Australia

Although central nervous system (CNS) cells are well known to functionally communicate via electrical and chemical signals, cell-surface glycans mediate the initial contact between cells and exogenous proteins. Glycans, carbohydrates bound to cellular membrane proteins, are prominently expressed on CNS cell-surface receptors (such as GPCRs), where they can be absolutely critical for receptor trafficking and function, as is the case for the angiotensin II AT1a receptor that regulates blood pressure. Membrane transporter expression and activity (such as crucial solute carrier family proteins that transport serotonin, dopamine, noradrenaline, GABA and glycine) are also highly affected by glycan expression. Cellular glycan expression is dynamic and is closely associated with the innate immune response as well as neuroinflammation driven by microglia. A unique recent concept in biomarker discovery has been to determine cell type-specific profiles through the characterisation of glycans. By characterising CNS cells in this way we could tailor nanotechnology and drug delivery vehicles towards individual CNS cell types with lectins, which can recognise highly specific glycan receptor structures. The in vivo application of lectins stimulates endocytosis of synaptic and/or somatic membrane glycolipids and subsequent trafficking to intracellular organelles such as endosomes and the endoplasmic reticulum. We are working to understand the cell-surface dynamics of CNS cells during inflammation using LC-MS to detect and quantify glycans and MS/MS to confirm the linkage structures of glycans on the surface of different CNS cells. Using this glycan profiling data, we have engineered lectin coated luminescent nanodiamonds and are testing their ability to recognise specific CNS cell types for imaging and drug delivery.