“Our work helps explain how brain cells communicate.”

This article in Nature describes, for the first time, modulation of synaptic transmission by a neurotransmitter receptor auxiliary subunit. This work has enjoyed unusually high impact because the auxiliary subunit, stargazin, modulates the function of AMPA type glutamate receptors, which are the major neurotransmitter receptor types in the brain.

This work represents an important and unexpected discovery. Previous work suggested that synaptic transmission by AMPA receptors was dictated only by the principle glutamate receptor subunits. Our work demonstrated that stargazin-type auxiliary subunits also play a fundamental role in shaping synaptic transmission.

Our work helps explain how brain cells communicate. The primary neurotransmitter used for this communication is glutamate. Our work shows that glutamate receptors do not work alone and that a new auxiliary subunit named "stargazin" also participates. Glutamate receptors mediate fundamental aspects of learning and memory and abnormal glutamate receptor function underlies several neurological and psychiatric diseases. Therefore, this work has broad implications.

Our team in this work, which includes, as full partner, Dr. Roger Nicoll at UCSF, became interested in stargazin, as this protein is mutated in "stargazer" mice. These mice suffer from absence epilepsy and cerebellar ataxia. These defects owe to a loss of functional AMPA receptors in specific neuronal types.

Our team determined that this loss of AMPA receptors reflects the fact that stargazin serves as an auxiliary subunit of neuronal AMPA receptors. The scientific community initially questioned this interpretation, as no other neurotransmitter-gated ion channels have known auxiliary subunits. However, this Nature article provides unequivocal proof.

Further studies of the stargazin gene family should provide insights into mechanisms controlling glutamate receptor function and synaptic transmission. This work has important implications for both science and medicine. Also, it will be important to learn whether other neurotransmitter receptors also have crucial auxiliary subunits.

As with any fundamental discovery regarding neuronal function, our work has significance for understanding brain physiology and disease. Because glutamate is the major neurotransmitter in the brain, one can anticipate diverse implications.