Killam Seminar Series: Posttranslational Palmitoylation in Brain Development and Disease
Supported by the generosity of the Killam Trusts, The Neuro's Killam Seminar Series invites outstanding guest speakers whose research is of interest to the scientific community at The Neuro and McGill University.
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Host: Edward Ruthazer
Posttranslational Palmitoylation in Brain Development and Disease
Shernaz Bamji
Professor, Department of Cellular and Physiological Sciences, University of British Columbia
Abstract: Palmitoylation is the most common post-translational lipid modification in the brain. This presentation focusses on the role of the palmitoylating enzyme, ZDHHC9, which has been strongly associated with X-linked intellectual disability (XLID). Patients with ZDHHC9 loss-of-function mutations exhibit reduced corpus callosum volume and impaired white matter integrity. Our work demonstrates that ablation of Zdhhc9 in mice substantially impairs the maturation of oligodendrocytes and results in a concomitant decrease in the density of myelinated axons. Ultrastructural analysis of the remaining myelinated axons in the corpus callosum revealed further disruptions in myelin integrity. Transcriptomic and proteomic analyses reveal decreased expression of genes and proteins crucial for lipid metabolism, cholesterol synthesis, and myelin compaction. Notably, Zdhhc9 knockout also disrupts axon outgrowth and pathfinding in the corpus callosum. These findings unveil a previously overlooked role for ZDHHC9 in governing oligodendrocyte maturation and myelinogenesis, and offers mechanistic insights into white matter volume deficits in patients with ZDHHC9 mutations.
Shernaz Bamji is a Professor in the Department of Cellular and Physiological Sciences at the University of British Columbia (UBC), where she also serves as co-Director of the Djavad Mowafaghian Center for Brain Health. She is a past President-elect of the Canadian Association for Neurosciences. Dr. Bamji completed her PhD under the mentorship of Dr. Freda Miller at the Montreal Neurological Institute (McGill University), investigating the role of BDNF in neuronal survival and death. She then moved to San Francisco and pursued postdoctoral research with Dr. Louis Reichardt at the University of California, San Francisco (UCSF), examining how cadherin adhesion molecules influence synapse formation and plasticity. Dr. Bamji’s research centers on the molecular and cellular mechanisms that govern brain development and neuronal connectivity. Her findings have deepened our understanding of the processes that underlie learning and memory, as well as how these processes are disrupted in disease.
