Evolutionary conservation of centriole rotational asymmetry in the human centrosome

Centrioles are formed by microtubule triplets in a nine-fold symmetric
arrangement. In flagellated protists and in animal 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 an ancient property of centrioles that is
broadly conserved in human cells. Our work also reveals that
asymmetrically localized proteins are key for primary ciliogenesis and
ciliary signaling in human cells.