Mechanosensations, including touch, hearing, proprioception, and mechanical nociception, are essential for animals to regulate their behaviors. Recently, TMC family proteins TMC1 and TMC2 have been widely studied for their role in mammalian hearing. Mutations of TMC1 and TMC2 lead to deafness in both humans and mice. TMC1 and TMC2 are most likely important components of mechanotransduction channels in the hair cells of our inner ear. However, their exact role has not yet been elucidated. Besides, whether TMC proteins function in other types of mechanosensations is not known.

　　In a recent paper entitled “Transmembrane channel-like (tmc) gene regulates Drosophila larval locomotion” publishedin PNAS USA on June 28th, the research teams of Dr. WANG Zuo-Ren at the Institute of Neuroscience and Dr. JAN Yuh-Nung at UCSF 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, the authors found that Drosophila tmc is expressed in the larval class I dendritic arborization neurons and bipolar dendrite neurons, both are known to provide sensory feedback for larval locomotion. Instead of hearing defects, they 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. Furthermore, expressing mammalian TMC1 and/or TMC2 with tmc-Gal4 driver rescued the behavioral defects caused by tmc mutation, suggesting functional conservation between Drosophila TMC and mammalian TMC proteins. This work suggests that TMC functions in mechanosensation in the body wall sensory neurons and regulates locomotion of Drosophila larvae.

　　This work was conducted by Dr. GUO Yanmeng, Dr. WANG Yuping, Dr. ZHANG Wei, Dr. MELTZER Shan, and Dr. ZANINI Damiano under thesupervision of Dr. WANG Zuo-Ren and Dr. JAN Yuh-Nung. This work was supported bythe StrategicPriority Research Program (B) of the Chinese Academy of Sciences (grant no. XDB02010005), and China 973 Project (grant no. 2011CBA0040)and NIH grants (R37NS040929 and 5R01MH084234).

　　Representative locomotion pattern (A) and locomotion trace (C) of wild type larvae. Representative locomotion pattern (B) and locomotion trace (D) of tmc mutant tmcGal4 larvae.