GPR55: A New Mediator of Axon Guidance
Material below summarizes the article Role of GPR55 During Axon Growth and Target Innervation, published on October 22, 2015, in eNeuro and authored by Hosni Cherif, Anteneh Argaw, Bruno Cécyre, Alex Bouchard, Jonathan Gagnon, Pasha Javadi, Sébastien Desgent, Ken Mackie, and Jean-François Bouchard.
Axons navigate in a complex environment with a multitude of external chemotactic cues that must be detected and effectively translated by a suitable growth response. The growth cone (GC) is the sensory structure at the axon tip that guides the axons in this landscape. Axon guidance cues help to establish functional neural circuits through guidance of axons to their specific targets during the development. At the GC surface, axon guidance molecules bind to their cognate receptors, triggering intracellular signaling cascades near the growth cone's cell membrane and downstream signal transduction pathways that converge on the cytoskeleton and cause axon steering and growth.
We identified, for the first time, the presence and the role of a G-coupled protein receptor called GPR55 in axon growth and segregation during the development of the visual system. Our results show that GPR55 and its ligand effect growth and axon guidance.
These findings will certainly have a significant impact in the field of neuroscience, mainly in the processes of the refinement and the target selection of neural circuits. Our research demonstrates both in vitro and in vivo that GPR55 and its ligands play a crucial role in the growth and axon steering of retinal projections to their brain targets.
In addition, the research provides a potential explanation of the enigmatic pharmacology of GPR55. Thus, the effect of its main endogenous ligand, lyso-phosphatidyl inositol (LPI), highly depends upon the concentration used. This explains the contradictory effects observed in the past by previous studies and offers a solution to better understand the effects of this receptor in different research areas. At low concentrations, this ligand increases axonal growth and produces an attractive effect via the ERK1/2 pathway. At higher concentrations, it yields to the opposite effect through the RhoA pathway.
A variety of biochemical, cellular, molecular, surgical, and microscopic methods were used in this study to better understand the impact of the genetic and pharmacological modulation of GPR55 on axon growth and guidance. This work is the result of a stimulating collaboration between two laboratories (Ken Mackie of Indiana University and Jean-François Bouchard of the University of Montreal). Several undergraduate, MSc, and PhD students, as well as postdoctoral fellows, participated in this research project.
Overall, this study provided valuable insights on the role and the function of GPR55 in axon growth and guidance of neuronal projections during the development. For all these reasons, this research is very interesting. However, further studies are needed to explore the potential implications of GPR55, and other GPCRs, in the development of novel therapies for neurological pathologies.
Role of GPR55 during Axon Growth and Target Innervation. Hosni Cherif, Anteneh Argaw, Bruno Cécyre, Alex Bouchard, Jonathan Gagnon, Pasha Javadi, Sébastien Desgent, Ken Mackie, and Jean-François Bouchard. eNeuro, Oct 2015, 2 (5) DOI: 10.1523/ENEURO.0011-15.2015