Differential regulation of transition zone and centriole proteins contributes to ciliary base diversity

Abstract

Cilia are evolutionarily conserved structures with many sensory and motility-related functions. The ciliary base, composed of the basal body and the transition zone, is critical for cilia assembly and function, but its contribution to cilia diversity remains unknown. Hence, we generated a high-resolution structural and biochemical atlas of the ciliary base of four functionally distinct neuronal and sperm cilia types within an organism, Drosophila melanogaster. We uncovered a common scaffold and diverse structures associated with different localization of 15 evolutionarily conserved components. Furthermore, CEP290 (also known as NPHP6) is involved in the formation of highly diverse transition zone links. In addition, the cartwheel components SAS6 and ANA2 (also known as STIL) have an underappreciated role in basal body elongation, which depends on BLD10 (also known as CEP135). The differential expression of these cartwheel components contributes to diversity in basal body length. Our results offer a plausible explanation to how mutations in conserved ciliary base components lead to tissue-specific diseases.

A theory of centriole duplication based on self-organized spatial pattern formation

“…We detected the peaks of the profiles and measured the angle (the distance in the profile plots) from each peak to its nearest neighbor to quantify the periodicity of the discrete ring patterns. Similar methods have been used successfully to analyze protein localization patterns in the ciliary transition zone or centriole distal appendages (Shi et al, 2017;Jana et al, 2018;Yang et al, 2018). The average angle between nearest-neighbor pairs was ∼60° (Fig.…”

An ancestral role of pericentrin in centriole formation through SAS-6 recruitment

“…We recently reported that SAS-6 not only constitutes the cartwheel structure but also is dynamically recruited to the spermatocyte BBs even after their cartwheel assembly. The later function of SAS-6 is required to elongate the BBs in the sperm cells (Jana et al, 2018). Here, our data suggest that pericentrin regulates the centriole length and stability by recruiting a part of the dynamic pool of SAS-6 to the centriole/BB.…”

“…SAS-6 is required for centriole biogenesis and recently implicated in centriole elongation (Hilbert et al, 2016;Jana et al, 2018). Therefore, we wondered in addition to STIL/Ana2 if pericentrin is indeed required for SAS-6 recruitment to the centriole and thereby its assembly and maturation in a multicellular organism, such as Drosophila.…”

A Theory of Centriole Duplication Based on Self-Organized Spatial Pattern Formation

“…We detected the peaks of the profiles and measured the angle (the distance in the profile plots) from each peak to its nearest neighbor to quantify the periodicity of the discrete ring patterns. Similar methods have been used successfully to analyze protein localization patterns in the ciliary transition zone or centriole distal appendages (Jana et al, 2018; Shi et al, 2017; Yang et al, 2018). The average angles between nearest-neighbor pairs were approximately 60° (Figure 2D).…”