Transmembrane channel-like (TMC) family proteins TMC1 and TMC2 have been studied for their role in mammalian hearing in recent years. They are most important components of mechanotransduction channels in the hair cells of our inner ear.

Mutations of TMC1 and TMC2 lead to deafness in both humans and mice. However, their exact role has not yet been elucidated. Besides, whether TMC proteins function in other types of mechanosensations, which are essential for animals to regulate their behaviors, is unknown.

Recently, the research teams led by Dr. WANG Zuoren at the Institute of Neuroscience (ION), Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences and Dr. JAN Yuh-Nung at University of California, San Francisco reported that Drosophila TMC regulates fly larval locomotion.

Locomotion requires peripheral sensory feedback from mechanosensitive proprioceptors. The molecular mechanisms underlying this proprioceptive locomotion control are largely unknown. This work likely sheds light on the molecular mechanisms underlying proprioception.

In this work, researchers found that Drosophila tmc is expressed in the larval class I dendritic arborization neurons and bipolar dendrite neurons. Both neurons are known to provide sensory feedback for larval locomotion.

Instead of hearing defects, researchers found tmc loss of function larvae mutants exhibited a reduction in crawling speed and an increase of head casts and backward locomotion. Expression of TMC with tmc-Gal4 driver rescued the behavioral defects caused by tmc mutation, whereas knocking down TMC led to similar behavioral defects as seen in tmc mutants. 

In addition, bending of the larval body activated the tmc-positive neurons, a response that was impaired in tmc mutants. Expressing mammalian TMC1 and/or TMC2 with tmc-Gal4 driver rescued the behavioral defects caused by tmc mutation.

This study suggests functional conservation between Drosophila TMC and mammalian TMC proteins and demonstrated TMC functions in mechanosensation in the body wall sensory neurons and regulates locomotion of Drosophila larvae.

The study entitled “Transmembrane channel-like (tmc) gene regulates Drosophila larval locomotion” was published in PNAS.

This study was supported by the Strategic Priority Research Program (B) of the Chinese Academy of Sciences, and National Basic Research Program of China (973 Program) and USA National Institutes of Health (NIH) grants.

Figure: Representative locomotion pattern (A) and locomotion trace (C) of wild type larvae. Representative locomotion pattern (B) and locomotion trace (D) of tmc mutant tmc^Gal4 larvae. (Image by Dr. WANG Zuoren)