Sticky protein boosts neuronal receptor’s response to anti-anxiety drugs

2019

Challenge

Sedatives called benzodiazepines are used to relieve anxiety, seizures, sleep disorders, and muscle spasms. For years, scientists thought these drugs worked alone to boost the inhibitory effects of neuronal GABA A receptors. However, it remained unknown whether these receptors contain additional factors that might determine how they function and travel across synapses, the communication junctions between neurons.

Advance

Using a variety of genetic and microscopic techniques in mice, IRP researchers led by senior investigator Wei Lu, Ph.D., discovered a protein, Shisa7, that ‘sticks’ to the GABA A receptor. From this position, Shisa7 controls how the receptor communicates across synapses, boosting the effect of benzodiazepines and thereby decreasing anxiety and increasing drowsiness.

Impact

GABA A receptors are affected by many therapeutic and recreational drugs. A better understanding of GABA A receptors and the influence of Shisa7 on their function may help researchers design and improve drugs that target GABA A receptors in order to treat neurological and neuropsychiatric disorders.

Publications

Han W, Li J, Pelkey KA, Pandey S, Chen X, Wang YX, Wu K, Ge L, Li T, Castellano D, Liu C, Wu LG, Petralia RS, Lynch JW, McBain CJ, Lu W. (2019). Shisa7 is a GABAA receptor auxiliary subunit controlling benzodiazepine actions. Science. Oct 11; 366(6462):246-250.