Fig. 1: Processing of native FPC generates C-terminal cleavage fragments in vivo, including ICD15 with an N-terminal mitochondrial targeting sequence. | Nature Communications

Fig. 1: Processing of native FPC generates C-terminal cleavage fragments in vivo, including ICD15 with an N-terminal mitochondrial targeting sequence.

From: Fibrocystin/Polyductin releases a C-terminal fragment that translocates into mitochondria and suppresses cystogenesis

Fig. 1: Processing of native FPC generates C-terminal cleavage fragments in vivo, including ICD15 with an N-terminal mitochondrial targeting sequence.The alternative text for this image may have been generated using AI.

a Diagram depicting the epitope positions of the anti-FPC antibodies, with PECD (magenta) and PTM (black) indicated. Figure created in BioRender. b Western blot of Pkhd1 KO, WT and HA P6 mouse kidneys using E1 (left panel) and anti-HA (right panel) antibodies. Various FPC products are indicated by (“a”–“f”), with corresponding ICD products marked by color-matched asterisks. Three independent experiments were performed, with similar results. c Western blot with E1. Six bands (“a”–“f”) are detected from WT (+) kidney lysates but not in lysates from knockout (-): The full-length (“a”), novel ~190 kDa band (“b”), PTM (“c”), and three small C-terminal bands at ~15 kDa (“d”), ~12 kDa (“e”), and 6 kDa (“f”) are indicated. A ladder of various low molecular weight constructs (MC to M-1) and the full-length FPC construct (FL) is used to map the size of the endogenous bands; their start sites are indicated in (d). Three separate experiments were performed, with similar results. d Functional motifs in mouse FPC C-terminal region. The predicted mitochondrial translocation sequence (MTS) is in red. The previously identified nuclear localization sequence (NLS)10 is blue and underlined. The transmembrane domain (TM) is enclosed in a box. The ciliary targeting sequence (CTS)9 is in green. The dashed box indicates the ICD15 region encoded by exon 67. The ladder construct start points are indicated for M-1 to MC for the ladder used in (c). e Sequence alignment of human and mouse FPC MTS. Non-identical amino acids are colored blue. p(Import): the probability of mitochondrial import. f Diagram of predicted FPC fragments indicating the position of the functional motifs and the Exon 67 encoded region, along with the labels of the respective bands. The predicted cleavage site in the extracellular domain is indicated. Figure created in BioRender. g Western blot of WT, +/-, ΔCT, and KO (-/-) P6 kidneys using E3, E4 and E1 antibodies. Loading control: β-Actin. Two separate experiments were performed, with similar results. Source data are provided as a Source Data file.

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