Sensory neurons play a critical role in perceiving sensations of “hot” and “cold.” They rely on thermosensitive TRP channels, such as TRPV1 (activated above 43°C) and TRPM8 (activated below 29°C), to relay this information to our brains. Recently, TRPV3, which responds to warm temperatures (32–39°C), has been identified in skin keratinocytes rather than sensory neurons. This sparked controversy over whether skin cells contribute to temperature sensing and if their responses can be transmitted to the brain.
To address this, a research group investigated TMEM79, a protein expressed in skin keratinocytes similar to TRPV3 but poorly understood. By overexpressing TRPV3 and TMEM79 in HEK293T cells, they observed that TRPV3-mediated currents were smaller when both proteins were present, suggesting TMEM79 reduces TRPV3’s activity.
In mice lacking TMEM79, temperature-dependent behaviors were altered. The mice preferred a warmer temperature than wild-type mice, indicating the loss of TMEM79 affected TRPV3-mediated currents in the skin, making the mice seek warmer environments.
Further studies revealed that TMEM79 caused TRPV3 to move from the plasma membrane to the cytosol, reducing TRPV3-mediated currents. Moreover, TMEM79 facilitated the transportation of TRPV3 to lysosomes, leading to TRPV3 degradation, which explained the decrease in TRPV3 proteins in cells co-expressing both proteins.
The research group concluded that TMEM79 controls temperature sensitivity in the skin by regulating the amount of TRPV3 proteins in skin keratinocytes. This discovery resolves the controversy about skin cells’ involvement in temperature detection and opens possibilities for regulating our temperature sensation by manipulating TRPV3 or TMEM79 function. Such findings could have potential applications in temperature-related therapies or interventions. The study was published in the journal Nature Communications.