Novel regulators of neural endosomes

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The proper development of the brain is a complex and finely-tuned process. There are widespread implications for learning and memory as well as the development of all sensory and motor functions. The cells in the brain that transmit information (neurons) undergo tremendous structural changes as they develop in order to set up connections within the brain and between the brain and the rest of the body. At the molecular level, an important protein family that my lab has recently identified as being involved in this process are the “pannexins”. The pannexins are known to form channels (like gated doors) in cell membranes that help allow passage of ions and metabolites that act as signals between cells. While the study of pannexins has previously focused on their role on the membranes at the surface of cells, we and others recently found that the pannexins are also found on the membranes of a specialized compartment inside the cell. This “endosome” compartment plays a key role in neurons during development by acting as a source of membrane required to build the new processes connecting neurons together (neurites). This compartment also regulates the functions of many of the other proteins (such as receptors) involved in directing the creation of neurites. The goal of this research program is to shed light on molecular factors governing the trafficking of pannexins to endosomes. Further, this will allow us to capitalize on this newly generated knowledge to determine the role of pannexins in regulating the basic properties and functions of endosomes in developing and mature neurons. Results from this work will make important contributions to new areas of knowledge development with respect to the distribution and roles of pannexins in neural cells, the regulation of the endosome compartment by ion and metabolite channels and the factors regulating the growth of neurites. These results will improve our understanding of the molecular mechanisms underlying critical brain activities like memory and learning.