Protein trafficking in neurons

The Arnold laboratory studies the molecular mechanisms underlying targeting of transmembrane proteins in neurons, concentrating on three main areas:

1. Polarized targeting: We have recently discovered a mechanism that provides a framework for understanding how proteins are targeted to the somatodendritic compartment in neurons.




2. Intrabodies: We are using mRNA display to generate recombinant antibodies that can be used to visualize the trafficking and localization of endogenous proteins in vivo. This work is being done in collaboration with Richard Roberts of the Chemistry department.




3. Light-activated proteins: By applying the principles of protein trafficking we are designing strategies to target light activated proteins such as Channel Rhodopsin to specific subcellular locations. This work is being done in collaboration with Karel Svoboda of the Janelia Farm Research Campus.

By arranging proteins in specific spatial distributions the cell can specify its shape, connectivity, and electrophysiological properties. For example, cells modulate protein localization to establishment synaptic connections during development, to modify them during learning and memory, and to respond to injury and disease.

Spatial distributions of the thousands of distinct neuronal proteins can be quite complex and are remarkably dynamic. A given protein molecule may spend only minutes in a particular location on the plasma membrane and has a lifetime of hours to days and yet despite the constant turnover of their  neurons must function seamlessly.