Native Piezo2 Interactomics Identifies Pericentrin as a Novel Regulator of Piezo2 in Somatosensory Neurons

The ability of somatosensory
neurons to perceive mechanical stimuli
relies on specialized mechanotransducing proteins and their molecular
environment. Only recently has the identity of a major transducer
of mechanical forces in vertebrates been revealed by the discovery
of Piezo2. Further work has established its pivotal role for innocuous
touch in mice. Therefore, Piezo2 offers a unique platform for the
molecular investigation of somatosensory mechanosensation. We performed
a mass spectrometry-based interactomics screen on native Piezo2 in
somatosensory neurons of mouse dorsal root ganglia (DRG). Stringent
and quantitative data analysis yielded the identity of 36 novel binding
partners of Piezo2. The biological significance of this data set is
reflected by functional experiments demonstrating a role for Pericentrin
in modulating Piezo2 activity and membrane expression in somatosensory
neurons. Collectively, our findings provide a framework for understanding
Piezo2 physiology and serve as a rich resource for the molecular dissection
of mouse somatosensation.