Every thought, feeling, memory, and sensation you have is dependent upon the function of the nervous system. The nervous system is made up of two primary cell types: neurons and glia. Glia are required to keep neurons healthy by helping them to acquire nutrients, dispose of wastes, for physical support, and insulating nerve fibers for efficient cellular communication. In contrast to the supporting (yet essential) role of glia, neurons are cells that are highly specialized for communication. Neurons are responsible for receiving and communicating information from the outside world to, and through the body. As such, neurons are extremely complex cells with a unique architecture and biochemical composition.
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 thus, the nervous system. Additionally, the architecture of the cell is such that the tip of the axon can be quite distant from the cell body where many of the cell’s components are made. Thus, neurons rely on an elaborate transport system to allow for the shipping of cellular components, such as membrane and secreted proteins, to distal sites within the cell.
A critical cellular cargo, called dense-core vesicles (DCVs), are responsible for the transport and secretion of a large group of neuropeptides, e.g. brain derived neurotrophic factor (BDNF), that are required for development, learning, memory, and neuronal survival. These molecules are packaged into DCVs in the Golgi apparatus then delivered to distal release sites via microtubule-based transport. Importantly, disruption of neuronal transport, including DCV transport, is a hallmark of neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Despite the importance of DCVs in neuronal function, little is known about the mechanisms mediating their transport. One goal of our lab is to characterize DCV transport and identify the motor proteins required for their transport to distal sites of release (Please see references 16, 17, 20). A second goal is geared towards understanding how faulty proteins implicated in Alzheimer’s disease disrupt fast axonal transport (Please see references 14, 18, 21).
From a technical standpoint, we combine molecular biology, immunocytochemistry, and cellular neuroscience. An integral tool for our research is the use of green fluorescent protein (GFP) to study protein transport in living neurons. These approaches provide numerous and varied research opportunities for students interested in working in my lab.
Finally, we greatly appreciate the funding we have received from the Natural Sciences and Engineering Research Council (NSERC) and the Canadian Institutes of Health (CIHR) that allows us to undertake this research.
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