To function properly, neurons need to transport molecules from their cell bodies to the projections called axons, but how this early-stage transportation system is organized is not well understood. In a new study, Yale neuroscientists asked: how does this neuronal molecular motor interact with its molecular cargo to deliver them to the axon along microtubule pathways?
Scientists have long been interested in the role played by End-binding protein 1 (EBP-1), which marks the end of microtubule. The protein has been heavily studied in cell culture but its function in living animals remained unknown.
"One of the main limitations was the lack of in vivo model," said Junhyun (Mick) Park, graduate student in Yale’s Interdisciplinary Neuroscience Program and first author of the paper. "Although [in vitro] studies have been extremely informative, it was not clear how important these proteins were in the neurons of a live animal," added Park.
To overcome this limitation, the team of researchers took advantage of the worm C. elegans, a model organism used to study the localization or function of proteins. "We were able to label these end-binding proteins and visualize them in our neuron of interest,” Park said.
In addition, the researchers were able to excise parts of native genes to study the function of EBP-1.
Interestingly, the researchers found that EBP-1 enables transport of neuropeptides in a subset of neurons.
The findings suggest that EBP-1 can facilitate recognition of cargo, which is the earliest, also the most understudied, step of any transport event.
Junhyun (Mick) Park
The findings were published August 15 in the journal Current Biology. Shaul Yogev, PhD, assistant professor of neuroscience and cell biology, and Pietro De Camilli, MD, John Klingenstein Professor of Neuroscience and professor of cell biology, are senior authors of the study.