Avital Rodal, Ph.D.
Assistant Professor
Brandeis University

Synaptic Growth: Signals on the Move

 

Dr. Avital Rodal, the newest member of the Brandeis neuroscience faculty, examines how neurons set up elaborate branches that are tailored to send and receive electrical signals over large distances and through complex networks of connections. These connections undergo dynamic structural and functional changes in response to external growth cues, which provides the basis for synaptic plasticity during both development and adulthood. The Rodal lab is focused on understanding how these growth cues are interpreted and manipulated within the cell and how their misregulation contributes to neurological disease.

Growth factors are received by membrane-bound cell surface receptors. Afterwards, the cell surface receptors are transported into the cell along with the pieces of membrane they are bound to. The membrane-associated receptors are then shuttled from one compartment to another. Interestingly enough, these growth factor receptors change their signaling properties depending on the compartment in which they are located. Therefore, the degree to which growth factor signaling occurs can be modulated based upon the rate at which these receptors move between compartments. These cellular events play a prominent role in the disease-related defects of Alzheimer's disease (AD) and Amyotrophic Lateral Sclerosis (ALS) and may also serve as a potential point of intervention for these diseases. The challenge is to understand how networks of hundreds of interacting membrane-deforming proteins, which are responsible for moving these receptors, are able to control cargo traffic. The Rodal lab seeks to understand how these proteins might themselves be regulated.

One powerful method to probe the cellular function of complex networks of interacting proteins is to visualize them in action using high-resolution microscopy wherein proteins of interest are fluorescently labeled. The Rodal lab is able to take advantage of recent advances in fluorescence microscopy that have opened new windows into cellular events within complex tissues. These advances have increased the speed and resolution at which rapid cellular dynamics can be recorded and analyzed. Dr. Rodal's group has used these new techniques to devise time-resolved trafficking assays for imaging membrane traffic in fruit fly neurons. The advantages of using the fruit fly system are that the components of the membrane traffic machinery are highly similar to their human counterparts, and that fruit flies can be genetically manipulated to express fluorescently tagged proteins allowing researchers to follow the dynamics of their protein of interest.

Dr. Rodal is also using the synapses that form between motor neurons and muscles (neuromuscular junctions) as a model. Using this system, the Rodal lab has shown that dynamic interactions between subcellular membrane compartments lead to the transfer of growth factor signaling receptor cargo from one compartment to another. The Rodal lab has also found that this transfer results in a reduction of receptor signaling activity and a concomitant reduction in neuronal growth. As a next step in these studies, the lab is developing new methods to image receptor traffic in more complex neuronal arbors in the central nervous system, as well as in fruit fly models of aging and neurodegenerative disease. By exploring the connection between disease states and growth-signaling pathways, the Rodal lab is uncovering specific changes in membrane traffic that occur during normal development and disease and that are important for neuronal growth and survival.