Re-evaluating TRP channel mechanosensitivity

Mechanotransduction is an evolutionary conserved and essential physiological process enabling cells to sense and convert mechanical stimuli into intracellular electrochemical events.Transient receptor potential (TRP) channels have been implicated in numerous mechanotransduction processes, including cancer cell migration, bone mineralization, and sensing blood flow.However, limited evidence supports TRP channels acting as primary mechanotransducers – those that directly sense and convert the external stimuli into an intracellular signal.Most evidence is congruent with TRP channels instead acting as molecular amplifiers responding downstream of the activation of a primary mechanotransducer (such as PIEZO1 or PIEZO2), forming mechanosensory modules.Here, we discuss the evidence supporting TRP channels as primary mechanotransducers and alternative models whereby TRP channels together with primary mechanotransducers could contribute to mechanosignalling. Transient receptor potential (TRP) channels are implicated in a wide array of mechanotransduction processes. However, a question remains whether TRP channels directly sense mechanical force, thus acting as primary mechanotransducers. We use several recent examples to demonstrate the difficulty in definitively ascribing mechanosensitivity to TRP channel subfamilies. Ultimately, despite being implicated in an ever-growing list of mechanosignalling events in most cases limited robust or reproducible evidence supports the contention that TRP channels act as primary transducers of mechanical forces. They either (i) possess unique and as yet unspecified structural or local requirements for mechanosensitivity; or (ii) act as mechanoamplifiers responding downstream of the activation of a primary mechanotransducer that could include Ca2+-permeable mechanosensitive (MS) channels or other potentially unidentified mechanosensors. Transient receptor potential (TRP) channels are implicated in a wide array of mechanotransduction processes. However, a question remains whether TRP channels directly sense mechanical force, thus acting as primary mechanotransducers. We use several recent examples to demonstrate the difficulty in definitively ascribing mechanosensitivity to TRP channel subfamilies. Ultimately, despite being implicated in an ever-growing list of mechanosignalling events in most cases limited robust or reproducible evidence supports the contention that TRP channels act as primary transducers of mechanical forces. Th