Evolutionary conservation of centriole rotational asymmetry in the human centrosome

Abstract

Centrioles are formed by microtubule triplets in a nine-fold symmetric arrangement. In flagellated protists and in multiciliated cells, accessory structures tethered to specific triplets render the centrioles rotationally asymmetric, a property that is key to cytoskeletal and cellular organization in these contexts. In contrast, centrioles within the centrosome of animal cells display no conspicuous rotational asymmetry. Here, we uncover rotationally asymmetric molecular features in human centrioles. Using ultrastructure expansion microscopy, we show that LRRCC1, the ortholog of a protein originally characterized in flagellate green algae, associates preferentially to two consecutive triplets in the distal lumen of human centrioles. LRRCC1 partially co-localizes and affects the recruitment of another distal component, C2CD3, which also has an asymmetric localization pattern in the centriole lumen. Together, LRRCC1 and C2CD3 delineate a structure reminiscent of a filamentous density observed by electron microscopy in flagellates, termed the acorn. Functionally, the depletion of LRRCC1 in human cells induced defects in centriole structure, ciliary assembly and ciliary signaling, supporting that LRRCC1 cooperates with C2CD3 to organizing the distal region of centrioles. Since a mutation in the LRRCC1 gene has been identified in Joubert syndrome patients, this finding is relevant in the context of human ciliopathies. Taken together, our results demonstrate that rotational asymmetry is a conserved ancient property of centrioles. Our work also reveals that asymmetrically localized proteins are key for primary ciliogenesis and ciliary signaling in human cells.

Human SFI1 and Centrin form a complex critical for centriole architecture and ciliogenesis

“…Such a radial structure has never been observed in the centriole, but it is likely that another type of assembly exists there. Indeed a recent study has shown that C2CD3 and LRRCC1 also localize at the lumenal distal end of the human centriole (Gaudin et al , 2022), similarly to SFI1 and Centrin, and delineate a structure reminiscent of the acorn, a filamentous density observed by electron microscopy in pro and mature Chlamydomonas basal bodies (Geimer, 2004; Gaudin et al , 2022). In addition, the acorn is accompanied by a V‐shaped filament system that has been proposed to be composed of Centrin (Geimer & Melkonian, 2005).…”

SFI1 and centrin form a distal end complex critical for proper centriole architecture and ciliogenesis

“…Such a radial structure has never been observed in the centriole, but it is likely that another type of assembly exists there. Indeed a recent study has shown that C2CD3 and LRRCC1 also localize at the luminal distal end of the human centriole (Gaudin et al, 2021), similarly to SFI1 and centrin, and delineate a structure reminiscent of the acorn, a filamentous density observed by electron microscopy in pro-and mature Chlamydomonas basal bodies (Gaudin et al, 2021;Geimer, 2004). In addition, the acorn is accompanied by a V-shaped filament system that has been proposed to be composed of centrin (Geimer and Melkonian, 2005).…”

Daughter centrioles assemble preferentially towards the nuclear envelope in Drosophila syncytial embryos

“…Intriguingly, LRRCC1 has recently been shown to localise asymmetrically within the lumen of human centrioles with the position of procentriole assembly being nonrandom with respect to this asymmetric mark (Gaudin et al, 2021). Thus, although the molecular nature may vary, it's possible that a non-random positional preference in daughter centriole assembly is an important conserved feature of centriole duplication.…”