Professor
(Massachusetts Institute of Technology
Woods Hole Oceanographic Institution)

Phone: 780-492-7180
Fax: 780-492-0450
Email: bob.campenot@ualberta.ca

Research Description

One of the major research directions in my laboratory is aimed at discovering the mechanism of retrograde neurotrophic factor signaling in neurons. Knowledge of this mechanism is extremely important because millions of connections between the axon terminals of neurons and their target cells (other neurons or sensory or effector cells) make up the electrical circuitry of the mammalian nervous system. Their formation during the development of the organism, and their maintenance in adults depends upon protein neurotrophic factors that are: released by the target cells, bind to receptors on the axon terminals, and generate intracellular signals that travel retrogradely to the cell bodies. The survival and proper functioning of neurons depends upon these basic mechanisms which are relevant to understanding and eventually treating neurodegenerative diseases such as Alzheimer’s disease and amyotrophic lateral sclerosis (ALS) and neurotrauma such as spinal cord and brain injury.

Our investigations utilize compartmented cultures, a technique that I invented in 1976. Axons growing from cell bodies in proximal compartments, cross silicone grease barriers to enter distal compartments, allowing the chemical environment of distal axons to be controlled and the composition of the distal axons to be analyzed separately from the cell bodies. Work by recent Ph.D. recipients from my laboratory, Darren Ure, Donna Senger, and Bronwyn MacInnis has provided strong evidence that retrograde signals do not require the retrograde transport to the cell bodies of signaling endosomes containing NGF bound to its receptor. Since this is the classic mechanism believed for almost 30 years, our discovery of alternative mechanisms has added an important dimension to this field. We are concentrating our efforts in this project on discovering the detailed mechanisms of the new forms of retrograde signaling. We also have an ongoing investigation into the mechanisms of axonal survival and a collaborative project with Drs. Jean Vance and Dennis Vance investigating lipid metabolism and function in neurons.

Selected Publications

Campenot R. B. and MacInnis B. L. (2004) Retrograde transport of neurotrophins: Fact and function. J Neurobiol 58, 217-229.

Hayashi H., Campenot R. B., Vance D. E. and Vance J. E. (2004) Glial lipoproteins stimulate axon growth of central nervous system neurons in compartmented cultures. J Biol Chem 279, 14009-14015.

Karten B., Vance D. E., Campenot R. B. and Vance J. E. (2003) Trafficking of Cholesterol from Cell Bodies to Distal Axons in Niemann Pick C1-deficient Neurons. J Biol Chem 278, 4168-4175.

MacInnis B. L. and Campenot R. B. (2002) Retrograde support of neuronal survival without retrograde transport of nerve growth factor. Science 295, 1536-1539.

Macinnis B. L. and Campenot R. B. (2005) Regulation of Wallerian degeneration and nerve growth factor withdrawal-induced pruning of axons of sympathetic neurons by the proteasome and the MEK/Erk pathway. Mol Cell Neurosci 28, 430-439.

MacInnis B. L., Senger D. L. and Campenot R. B. (2003) Spatial requirements for TrkA kinase activity in the support of neuronal survival and axon growth in rat sympathetic neurons. Neuropharmacology 45, 995-1010.

Senger D. L. and Campenot R. B. (1997) Rapid retrograde tyrosine phosphorylation of trkA and other proteins in rat sympathetic neurons in compartmented cultures. J Cell Biol 138, 411-421.

Postdoctoral Fellow

Dr. Sue Ann Mok

Technician

Karen Lund