Synaptic Activity–Dependent Changes in the Hippocampal Palmitoylome
This week we profile a recent publication in Science Signaling from the lab of Dr. Shernaz Bamji (pictured, left) with first authors Glory Nasseri (centre) and Dr. Nusrat Matin (right) from the Life Sciences Institute and Djavad Mowafaghian Centre for Brain Health.
Can you provide a brief overview of your lab’s current research focus?
Our lab is working to understand the molecular mechanisms by which the connections between brain cells, known as synapses, are formed, remodeled and eliminated. Synaptic remodeling happens throughout life in the brain and is a critical process that allows us to learn and store new information. The primary focus of our lab at present is to determine how the addition and removal of a fatty acid lipid molecule, in a process known as ‘protein palmitoylation’, alters the function of key proteins that are involved in signaling at the synapse. We hope to better understand the critical role of palmitoylation in synaptic remodeling, and how disrupted palmitoylation contributes to numerous brain disorders, including Schizophrenia and X-linked intellectual disability.
What is the significance of the findings in this publication?
We used an unbiased molecular technique known as proteomics to uncover a list of proteins that are differentially modified by palmitoylation in the mouse hippocampus during learning. The findings of this publication suggest that regulated palmitoylation modulates changes in synaptic transmission that underlie hippocampal memory. As the hub for contextual memory, enhancement or suppression of palmitoylation specifically in the hippocampus may contribute to associative learning. These findings highlight novel networks of dynamically palmitoylated proteins involved in learning and memory processes that may be disrupted in neurological disorders, such as Schizophrenia and Alzheimer’s disease.
What are the next steps for this research?
Now that we have identified a list of synaptic proteins that are regulated by palmitoylation, the next steps are to investigate how this altered palmitoylation changes the function of these proteins, how changes in palmitoylation affect the ability of synapses to participate in learning and memory, and which of the family of enzymes that regulate palmitoylation at the synapse are driving these changes.
If you’d like to mention your funding sources, please list them.
This work was supported by grants from Canadian Institutes of Health Research (to Shernaz X. Bamji), and Genome Canada and Genome BC (to Leonard J. Foster).