WDR90 is a centriolar microtubule wall protein important for centriole architecture integrity

Abstract

27Centrioles are characterized by a nine-fold arrangement of long-lived 28 microtubule triplets that are held together by an inner protein scaffold. These 29 structurally robust organelles experience strenuous cellular processes such as cell 30 division or ciliary beating while performing their function. However, the molecular 31 mechanisms underlying the stability of microtubule triplets, as well as centriole 32 architectural integrity remain poorly understood. Here, using ultrastructure expansion 33 microscopy (U-ExM) for nanoscale protein mapping, we reveal that POC16 and its 34 human homolog WDR90 are components of the centriolar microtubule wall along the 35 central core region of the centriole. We further found that WDR90 is an evolutionary 36 microtubule associated protein with a predicted structurally homology with the ciliary 37 inner junction protein FAP20. Finally, we demonstrate that WDR90 depletion impairs 38 the localization of inner scaffold components, leading to centriole structural 39 abnormalities in both human and Chlamydomonas cells. Altogether, this work 40 highlights that POC16/WDR90 is a crucial evolutionary conserved molecular player 41 participating in centriole architecture integrity. 42 43 44 45

Structural bioinformatics predicts that the Retinitis Pigmentosa-28 protein of unknown function FAM161A is a homologue of the microtubule nucleation factor Tpx2

“…The molecular basis for that binding has previously been unknown, but the findings here provide models for this interaction. Given that another cylindrical layer containing WDR90 is proposed to lie between the FAM161A layer and microtubules ( Steib et al , 2020 ), FAM161A may only be able bind microtubules through gaps in the WDR90 layer. This might explain how evolution has produced small microtubule-binding domains of short loops and helices ( Figure 4 ).…”

Biophysical and Quantitative Principles of Centrosome Biogenesis and Structure

“…Several studies have reported the existence of a cylindrical sheet of material running along the centriole lumen and connecting all the A-tubules (Geimer & Melkonian 2004, Vorobjev & Chentsov 1982. Indeed, along the centriole length, the pinhead is replaced by an inner centriole scaffold that is involved in stabilizing the centriole barrel (Le Guennec et al 2021, Steib et al 2020) (Figure 1c). Recently, Le Guennec and colleagues (2020) described its ultrastructural organization (Figure 1c), revealing the evolutionary conservation of the inner scaffold despite its species-specific differences.…”

A Proximity Mapping Journey into the Biology of the Mammalian Centrosome/Cilium Complex

“…Centrioles are not just hollow, empty barrels; instead, about 70% of their lumen contains an inner helical scaffold that forms a dense lattice by interconnecting the microtubule triplets [15,26]. Recent studies suggested structural functions for the inner core in the maintenance of centriole microtubule triplet cohesion and geometry [15,27]. Application of Ultrastructure Expansion Microscopy (U-ExM) to the centriole inner core identified and mapped POC5, POC1B, Centrin-2, FAM161A and WDR90 as the five components of a microtubule-associated complex associated with the helical scaffold [27].…”

“…Recent studies suggested structural functions for the inner core in the maintenance of centriole microtubule triplet cohesion and geometry [15,27]. Application of Ultrastructure Expansion Microscopy (U-ExM) to the centriole inner core identified and mapped POC5, POC1B, Centrin-2, FAM161A and WDR90 as the five components of a microtubule-associated complex associated with the helical scaffold [27]. In addition to the inner core, the molecular and structural code of the distal appendages were also unraveled by with nanoscale precision [23,25,28].…”