FIGURE 6.

Model of the composition of the C1d projection in humans. a) Based on our immunofluorescence analyses using anti-CFAP46 antibodies, CFAP46, CFAP54 and CFAP74 form a heterotrimeric subcomplex (grey) within the human wild-type C1d projection. CFAP221 (blue) also belongs to the C1d projection but seems not to be directly involved in this heterotrimeric subcomplex, resembling findings in Chlamydomonas reinhardtii and indicating evolutionary conservation of the C1d projection. Our immunofluorescence analyses reveal the following. b) In a CFAP46-variant individual, CFAP46 is undetectable. c) In CFAP54-variant individuals, CFAP46 is not detectable, indicating that the CFAP46 assembly is dependent on functional CFAP54. d) In CFAP74-variant individuals, CFAP46 appears reduced within the ciliary axoneme, revealing that CFAP74 is involved in the assembly of CFAP46. e) In a CFAP221-variant individual, CFAP46 is not affected, which suggests a distal position of CFAP221 within the C1d projection. (Proteins directly affected by biallelic pathogenic variants are crossed out. Impaired protein assembly is illustrated by a white area with a grey border.)