An alpha7/Gprin1 Interaction

Images of At nAChR and Gprin1

Jacob Nordman, a Ph.D. candidate working in the Kabbani Lab of the Krasnow Institute at George Mason University spoke on his research on α7 nicotinic acetylcholine receptor (nAChR) and G protein regulated-inducer of neurite outgrowth 1 (Gprin1) interactions which regulates axon growth and growth cone within hippocampal neurons. The α7 nAChR is a ligand gated calcium channel, which are abundantly expressed within the developing and adult hippocampus. 

 The main focus of this research includes the goal to study the proteome and their relation to dopamine and nicotinic acetylcholine receptors in the nervous system.  Studying their relation is significant in brain functioning such as memory, and cognition that could furthermore help us to understand of developing drugs for the treatment of several brain disorders like Alzheimer’s disease, Parkinson’s disease, and Schizophrenia.

The structure of the Growth Cone

 Nordman explained the Ionotropic and metabotropic division, and their study between the interaction of α7 and Gprin1. He then focused his topic on the growth cone that plays critical role in guiding axonal development and wiring of neuronal circuit. It is a complex structure of three layers: central zone (forearm), transitional zone (palm of hand) and peripheral (fingers). Together they make up arm, which pulls the growth cone along to its final destination that guides axon development. The seven states that take place in axonal development are initiation, formation, guidance, branching, turning, arrest and retraction.

Molecular model of the alpha7 nicotinic receptor.

His research have found that α7and Gprin1 are enriched in the soma and growth cones. To prove the interaction of α7 and Gprin1 in growth cones, transfection was done to insert α7 nAChR into Neuro-2a cells, which are neuron-like cells that produce only Gprin1, followed by immunoprecipitation, in which Gprin1 was removed from Neuro-2a cells. As a result of removing Gprin1, the link between α7  nAChR and Gprin1 was weakened, suggesting that they are present in growth cones and have interaction between two.

Consequently Nordman concluded his presentation that in “active state” filopodia of the growth cone project in all direction. It commits to a direction through microtubule invasion of collapse of filopodia. α7 activation inhibits G proteins mediated pathways involved in growth. The sum effect is microtubule capping and growth cone collapse.

 

Hence, these findings contribute in helping us to understand signaling cascades, new drug targets, plasticity mechanisms, greater-inter connectivity and many more functions we have not discovered yet. As a result, this makes us wonder that since α7and Gprin1 on the growth cone plays critical role in guiding axonal development and wiring of neuronal circuit, could it play greater role in treating or curing neurological disorders?