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Faculty of Graduate Studies

Annika Ariano

  • B.Sc. (University of Guelph, 2023)
Notice of the Final Oral Examination for the Degree of Master of Science

Topic

Detailed examination of the PANX1-ARP3 interaction in the context of wildtype and variant PANX1

School of Medical Sciences

Date & location

  • Friday, August 14, 2026
  • 1:00 P.M.
  • Medical Sciences Building, Room 150

Examining Committee

Supervisory Committee

  • Dr. Leigh Anne Swayne, School of Medical Sciences, University of Victoria (Supervisor)
  • Dr. Brian Christie, School of Medical Sciences, UVic (Member)
  • Dr. Nicole Templeman, Department of Biology, UVic (Outside Member)

External Examiner

  • Dr. Lisa Reynolds, Department of Biochemistry and Microbiology, UVic

Chair of Oral Examination

  • Dr. Justin Albert, Department of Physics and Astronomy, UVic

Abstract

Neurodevelopment is a critical process that lays the foundation for the brain’s structure and function, which are essential for cognition, emotion, and behaviour. Due to the highly complex nature of neurodevelopment, it is crucial that it be highly regulated through the coordination/interaction of signalling pathways and biological molecules. Pannexin1 (PANX1), a transmembrane protein primarily involved in ATP release, has been associated with several neurodevelopmental processes through its most widely known role as a channel protein, as well as through its lesser-known channel-independent functions, which include signalling hub and scaffolding roles. PANX1s channel-independent functions allow it to interact with different proteins of the cell, including cytoskeletal and cytoskeleton-associated proteins, that work together to change cell shape among other cellular processes implicated in neurodevelopment. Based on research from our lab and others, PANX1 has been shown to negatively regulate dendritic spine and neurite stability, suggesting a role for PANX1 in regulating cytoskeletal dynamics. Notably, our lab previously discovered an interaction between PANX1 and actin-related protein 3 (ARP3), an actin nucleating protein, which we hypothesize to be one of several molecular interactions involved in PANX1s negative regulation of neurite/dendritic spine stability. Using mouse Neuro-2a cells as a cellular model, we are now aiming to classify the interaction between PANX1 and ARP3, with the goal of furthering our understanding of how these two proteins interact at a molecular level. Furthermore, since both PANX1 and ARP3 have been implicated in several neurodevelopmental disorders associated with neurite and dendritic spine abnormalities, we suspect that the PANX1 variants identified in individuals with polymicrogyria (PMG; a malformation of cortical development) may be disrupting the PANX1-ARP3 interaction and subsequent neurite formation, causing the structural and developmental abnormalities observed in these patients. Overall, I found that the PANX1-ARP3 interaction in N2a cells occurs through PANX1s distal CT and seems to be indirect, and that PANX1 does not affect ARP3 subcellular localization at a broader level. By examining the PANX1-ARP3 interaction, this study advances our understanding of PANX1s physiological and pathophysiological roles in neural cells in the context of its influence on dendritic spine and neurite formation, while also shedding light on the underlying molecular mechanisms involved.

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