Protein trafficking in cultured hippocampal neurons

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Neurons are the building block of the nervous system and the primary role of the neuron is to act as an information processor. The neuron's function is intimately linked to its form, or morphology. Neurons are morphologically and biochemically asymmetric, or polarized cells, containing two primary domains: the axon and the somatodendritic domain. Axons are responsible for the transmission of information and dendrites receive and decode information from neighboring cells. Establishing these two domains is critical in building a neuron, and the nervous system. Additionally, the architecture of the cell is such that the tip of the axon can be quite distant form the cell body where many of the cell's components are made. Thus, neurons rely on an elaborate intracellular transport system to allow for the shipping of cellular components, such as proteins, to distal sites within the cell. Two primary pathways in which proteins are processed in the cell are through the biosynthetic pathway either via the constitutive route, which primarily involves transmembrane proteins, and the secretory route, which involves the processing and regulated release of soluble proteins. In general, both types of proteins are sorted into carrier vesicles in the Golgi apparatus, transported along microtubules, and finally delivered to the plasma membrane for either addition to the plasma membrane or release from the cell. This grant has two main foci.  One major aim is to understand how the cell targets membrane proteins to the dendrites. The other major aim is to understand what microtubule-based motor proteins are responsible for the transport of dense core vesicles. Finally, there are several examples of human and animal diseases where the underlying cellular defect relates to problems in protein trafficking. Thus, understanding the basic aspects of protein trafficking and nerve cell biology will significantly advance our understanding of the causes of neurodegenerative disorders like Lou Gehrig's and Alzheimer's disease.