Heat- and PIP2-dependent TRPM4 activity underlies mutually exclusive human diseases - PubMed
3 hours ago
- #PIP2 regulation
- #TRPM4 channels
- #Temperature sensitivity
- TRPM4 ion channels convert intracellular calcium increases into membrane depolarization, linking calcium signaling and membrane excitability.
- PIP2 lipid is a required cofactor for TRPM4 activity, regulating its calcium sensitivity via two binding sites.
- Skin disease-associated TRPM4 mutations relieve PIP2 control, elevating channel activity specifically at body surface temperatures.
- Heart disease-associated mutations increase channel number but are annihilated by desensitization outside body core temperatures.
- Transgenic mice with skin disease mutants showed elevated dendritic cell migration at 25-30°C, but no difference at 37°C.