Pannexin 1 in Neurodevelopment, Neurological Disease, and Brain Aging
Neurons – the information-transmitting cells in our brains – communicate at specializations called synapses consisting of pre- and post-synaptic elements. We have recently shown that the ATP-release channel pannexin 1 (PANX1) regulates the stability and density of post-synaptic structures called dendritic spines. Based on these initial findings, we have good reason to believe that processes that alter PANX1 levels – such as inflammation or injury – could have important implications for dendritic spines, and therefore synapses. This area of research investigates the mechanisms underlying PANX1 regulation of dendritic spines in development, disease and aging and involves several biochemical and advanced microscopy techniques. Related to this work, we are also studying the intercellular interactions and molecular mechanisms regulating PANX1 trafficking and expression levels, as well as PANX1 regulation of cytoskeletal dynamics. Understanding how PANX1 regulates synapses, and how neuron-glial cell interactions are implicated in this regulation, will provide key insights into neurological disorders affecting these critical structures.
Swayne lab team members: Dr. Leigh Wicki-Stordeur, Haifei You, Joel Rivera, Malia Copley
Collaborators: Dr. Keith Murai, Dr. Sabrina Chierzi (McGIll)
Selected publications:
- Foundations and implications of astrocyte heterogeneity during brain development and disease.
- Purinergic signaling in nervous system health and disease: Focus on pannexin 1.
- Pannexin 1 Regulates Dendritic Protrusion Dynamics in Immature Cortical Neurons.
- Pannexin 1 Regulates Network Ensembles and Dendritic Spine Development in Cortical Neurons.
- Probenecid Disrupts a Novel Pannexin 1-Collapsin Response Mediator Protein 2 Interaction and Increases Microtubule Stability.
- A novel motif in the proximal C-terminus of Pannexin 1 regulates cell surface localization.
Ankyrin-B in Heart and Brain Cell Biology
Ankyrin-B (AnkB) is a scaffolding protein that localizes transmembrane proteins regulating ion fluxes in heart and brain cells. Not only are these ion fluxes critical for proper heart and brain cell function, they can also regulate cellular development and differentiation. In this area of research, we are investigating the hypothesis that AnkB regulates heart and brain cell development, and that disease-associated AnkB variants could impact on these processes. We will capitalize on our expertise in biochemistry and microscopy to address our research questions. The outcomes of this work will help advance understanding of the role of AnkB in heart and brain development, function and disease.
Swayne lab team members: Nicole York, Joel Rivera, K’sana Wood Lynes-Ford, Malia Copley
Collaborator: Dr. Laura Arbour (UVic, UBC)
Selected publications:
- Mechanisms underlying the role of ankyrin-B in cardiac and neurological health and disease.
- Ankyrin-B p.S646F undergoes increased proteasome degradation and reduces cell viability in the H9c2 rat ventricular cardiomyoblast cell line.
- Ankyrin B and Ankyrin B variants differentially modulate intracellular and surface Cav2.1 levels.
- Novel Variant in the ANK2 Membrane-Binding Domain Is Associated With Ankyrin-B Syndrome and Structural Heart Disease in a First Nations Population With a High Rate of Long QT Syndrome.
Understanding the Impact of COVID-19 on the Brain
The Swayne lab is investigating the impact of COVID-19 on the brain.
Swayne lab team members: Dr. Leigh Wicki-Stordeur, Mohammadreza Rahmani Manesh, Mary Warren, Mareya Valeva
Collaborators: Dr. Marie-Eve Tremblay (UVic) and Dr. Darwyn Kobasa of the National Microbiology Laboratory/PHAC
Collaborative Work on Host-Pathogen Interactions
Dr. Swayne has also assisted Dr. Caroline Cameron‘s group in their investigation of the nature and functional consequences of T. pallidum molecular interactions with host cells.
Publications:
- Treponema pallidum Disrupts VE-Cadherin Intercellular Junctions and Traverses Endothelial Barriers Using a Cholesterol-Dependent Mechanism.
- Identification of the Neuroinvasive Pathogen Host Target, LamR, as an Endothelial Receptor for the Treponema pallidum Adhesin Tp0751
We are grateful for funding from the Natural Sciences and Engineering Research Council of Canada the Canadian Institutes of Health Research, and the Dr. Alfred “Fred” Fischer Memorial Fund.