Regulation of Hair Shedding by the Type 3 IP3 Receptor

The study demonstrated that the type 3 IP3 receptor (IP3R3) is crucial for hair cycle regulation, as evidenced by IP3R3-deficient (Itpr3(-/-)) mice exhibiting significant alopecia due to disrupted hair cycle regulation, with hair loss and regrowth occurring in a wave-like pattern. These mice showed normal hair growth and cell proliferation in the anagen phase, but their telogen club hairs were not as securely attached to the hair follicles as in normal mice (Itpr3(+/+)), leading to easier shedding. The keratinocytes in Itpr3(-/-) mice had disorganized cytokeratin filaments and underdeveloped desmosomes, and there was a failure in the nuclear translocation of NFATc1 in bulge cells during the telogen phase. The study suggests that hair shedding is regulated by the IP3R3/NFAT signaling pathway, which may influence the organization of cytokeratin filaments in keratinocytes.