In particular, the technique may be used to develop a range of fluorescent sensors to visualize neuronal self-connectivity, which is implicated in brain conditions such as autism and epilepsy.
The sensors developed in this study have many potential applications. "The development of IPAD is an important step toward a better understanding of the neuronal recognition of self/other." "Despite its current drawbacks, we think that our new sensor will be useful for a number of different research applications," explains Tomoki Matsuda, senior author of the study. For example, its fluorescence is much duller than that observed using older techniques, and it is unable to differentiate connections between processes from the same cell and those from two different cells with the same combinations of Pcdh on the surface. This new technique does have a few disadvantages. "This sensor allows us to see not only interactions between processes, but also the dissociation of these interactions for the first time." "We developed a fluorescent-based sensor that we named IPAD, or Indicators for Protocadherin Alpha 4 interactions upon Dimerization," says lead author of the study Takashi Kanadome. Researchers from Osaka University wanted to tackle this issue. Although there are conventional techniques for detecting molecular interactions between cell surfaces, which can show us when the molecules bind, but not when they split apart again.
Conversely, if the combinations are even slightly different, they are viewed as "other" rather than "self," and do not bind. One role of Pcdh is in cell adhesion if two neuronal processes have exactly the same combination of Pcdh molecules, the molecules bind to one another. One way to avoid this involves Pcdh, which is expressed in different combinations on each neuron's surface. However, because each cell has so many processes all over the place, cells can accidentally make connections with themselves rather than with others. To do so, each neuron puts out tiny processes that grow and travel until they find another cell's processes to connect with. In the brain, millions of neurons make trillions of connections with each other. In a recent publication in iScience,researchers from SANKEN (The Institute of Scientific and Industrial Research) and the Graduate School of Frontier Biosciences at Osaka University reported the development of a sensor to look at Pcdh interactions in live neurons, which brings us closer to understanding this mystery.
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