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. 2021 Jan 14;8:601006. doi: 10.3389/fcell.2020.601006

FIGURE 1.

FIGURE 1

Klotho includes different isoforms and binds to FGFR, facilitating the binding and subsequent signal transduction of FGF23. (A) The KL gene encodes a single-pass transmembrane protein, comprising an N-terminal short signal sequence (S), the ectodomain, containing the internal repeats KL1 and KL2, the transmembrane domain (TM), and a short cytoplasmic domain (CYT). It exists as full-length 135-kDa membrane-bound KL, the 130-kDa shed soluble KL (sKL) isoform, and the truncated secreted variant of KL. Proteolytic cleavage of full-length KL due to α-cut and/or β-cut produces sKL, containing either KL1, KL2, or both. Alternative RNA splicing of KL mRNA generates the secreted isoform, containing an N-terminal signal sequence and KL1 only. (B) The complexation of KL with FGFR enables the binding of FGF23, resulting in the formation of a trimeric complex, which activates the downstream signaling pathway. Created with BioRender.com.