This week we profile a recent publication in eLife from the lab of Dr. Kota Mizumoto (pictured, back row, second from left) with first author Ardalan Hendi (back row, third from left) at UBC.
Can you provide a brief overview of your lab’s current research focus?
In the nervous system, nerve cells communicate with other cells via specialized interfaces called synapses. The position and number of synapses must be tightly regulated for the nervous system to function properly, and many neurological diseases are associated with aberrant synapse numbers and connections. The Mizumoto lab is trying to uncover genetic and molecular mechanisms that underlie precise synapse numbers/positions using nematode (Caenorhabditis elegans) as a model organism. While C. elegans has a simple nervous system with 302 neurons, but genes and proteins that are necessary for nervous system development and function are highly similar to those in mammals, including humans, making it an ideal genetic model to understand how each nerve cell determines the number and position of synapses.
What is the significance of the findings in this publication?
In addition to synapses, nerve cells use another interface called a gap junction to communicate with other cells. Gap junction is a complex of proteins called Pannexins in vertebrates and Innexins in invertebrates, and they form a channel between cells for exchanging small molecules and ions. In our latest work, we uncovered an unexpected role for Innexin as a negative regulator of synapse formation. In the loss of function mutant of the C. elegans innexin gene (unc-9), we observed excessive synapse formation. Surprisingly, we did not observe excessive synapse when we genetically manipulated the channel activity of the UNC-9-gap junction. We propose that UNC-9 gap junction protein has a novel channel-independent function as a negative regulator of synapse formation.
What are the next steps for this research?
In our present work, we could not identify how the UNC-9 gap junction protein controls synapse number. In order to apply our knowledge to the mammalian nervous system, it is important for us to understand the molecular mechanisms by which the UNC-9 gap junction protein controls synapse number. We can then test if the same mechanism is present in mammals.
We know that gap junctions are very important cellular interfaces in our nervous system, yet they aren’t well studied compared to synapses. For instance, we know very little about how the position and number of gap junctions are controlled. As C. elegans gap junctions can be visualized easily in live animals, we hope to identify genetic and molecular mechanisms that govern gap junction locations and positions.
If you’d like to mention your funding sources, please list them.
This work is supported by HFSP (CDA-00004–2014), CIHR (AWD-017638), and CIHR (PJT- 180563)
