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Protein kinase A activation promotes plasma membrane insertion of DCC from an intracellular pool: A novel mechanism regulating commissural axon extension.

Author	Jean-François Bouchard, Simon W Moore, Nicolas X Tritsch, Philippe P Roux, Masoud Shekarabi, Philip A Barker, Timothy E Kennedy
Citation Information	The Journal of neuroscience : the official journal of the Society for Neuroscience, 24:3040-50 (2004)
Keywords	Adenylate Cyclase, Animals, Axons, Cell Adhesion Molecules, Cell Adhesion Molecules, Neuronal, Cell Membrane, Cells, Cultured, Cyclic AMP, Cyclic AMP-Dependent Protein Kinases, Enzyme Activation, Enzyme Inhibitors, Exocytosis, Intracellular Fluid, Nerve Growth Factors, Neural Cell Adhesion Molecules, Protein Transport, Rats, Rats, Sprague-Dawley, Receptor, trkB, Spinal Cord, Tumor Suppressor Proteins
Related Products	AB306, AB5032
Pub Med ID	15044543

Protein kinase A (PKA) exerts a profound influence on axon extension during development and regeneration; however, the molecular mechanisms underlying these effects of PKA are not understood. Here, we show that DCC (deleted in colorectal cancer), a receptor for the axon guidance cue netrin-1, is distributed both at the plasma membrane and in a pre-existing intracellular vesicular pool in embryonic rat spinal commissural neurons. We hypothesized that the intracellular pool of DCC could be mobilized to the plasma membrane and enhance the response to netrin-1. Consistent with this, we show that application of netrin-1 causes a modest increase in cell surface DCC, without increasing the intracellular concentration of cAMP or activating PKA. Intriguingly, activation of PKA enhances the effect of netrin-1 on DCC mobilization and increases axon extension in response to netrin-1. PKA-dependent mobilization of DCC to the plasma membrane is selective, because the distributions of transient axonal glycoprotein-1, neural cell adhesion molecule, and trkB are not altered by PKA in these cells. Inhibiting adenylate cyclase, PKA, or exocytosis blocks DCC translocation on PKA activation. These findings indicate that netrin-1 increases the amount of cell surface DCC, that PKA potentiates the mobilization of DCC to the neuronal plasma membrane from an intracellular vesicular store, and that translocation of DCC to the cell surface increases axon outgrowth in response to netrin-1.