The Molecular Mechanisms of Glycolytic Enzyme Palmitoylation
Neuronal axons can be over a meter long, making the efficient transport of proteins, organelles, and vesicles a challenge. Axonal transport is critical for neuronal function and trafficking deficits are prevalent in neurodegenerative disorders. Glycolytic enzymes provide the energy required for transport and are attached to fast transport vesicles that are propelled by motor proteins. But how do these soluble, cytosolic enzymes attach to fast moving vesicles? I discovered that a post-translational modification, palmitoylation, may hold the answer. I hypothesized that palmitoylation acts as a tether, attaching the enzymes to transport vesicles where they provide "on-board" energy for transport. I found that 8/10 glycolytic enzymes are palmitoylated. I pinpointed the palmitoylation site of GAPDH at cysteine 247 and observed a decrease in vesicle localization of palmitoylation deficient GAPDH. Unlocking the mechanisms behind this process not only improves our understanding of neuron function, but also has the potential to shed light on complex behaviors like learning and memory.