The complexity of the cilium: spatiotemporal diversity of an ancient organelle

Abstract

Cilia are microtubule-based appendages present on almost all vertebrate cell types where they mediate a myriad of cellular processes critical for development and homeostasis. In humans, impaired ciliary function is associated with an ever-expanding repertoire of phenotypically-overlapping yet highly variable genetic disorders, the ciliopathies. Extensive work to elucidate the structure, function, and composition of the cilium is offering hints that the `static' representation of the cilium is a gross oversimplification of a highly dynamic organelle whose functions are choreographed dynamically across cell types, developmental, and homeostatic contexts. Understanding this diversity will require discerning ciliary versus non-ciliary roles for classically-defined `ciliary' proteins; defining ciliary protein-protein interaction networks within and beyond the cilium; and resolving the spatiotemporal diversity of ciliary structure and function. Here, focusing on one evolutionarily conserved ciliary module, the intraflagellar transport system, we explore these ideas and propose potential future studies that will improve our knowledge gaps of the oversimplified cilium and, by extension, inform the reasons that underscore the striking range of clinical pathologies associated with ciliary dysfunction.

FIGURE 1:. HuRI-generated protein-protein interaction networks for IFT-B components.

The Human Reference Protein Interactome (HuRI) Mapping Project (http://interactome.baderlab.org/) identifies binary protein-protein interactions using yeast two-hybrid as the primary screening method. For the interaction networks, the red circles denote the analyzed IFT-B members while the blue circles indicate interacting proteins. Interactors with known ciliary associations are denoted with a yellow star. Interactions are characterized with different colored lines indicating variable levels of validation: green lines (published interaction; at least two pieces of experimental evidence of which at least one stems from a binary interaction detection assay), orange lines (validated interaction; interactions that are not yet published but originate from datasets that have been validated by successfully testing a representative subset of these interactions in at least one orthogonal binary interaction detection assay), red lines (verified interaction; interactions that are neither published nor validated but were identified in pooled yeast two-hybrid (Y2H) screens, tested positive in Y2H pairwise test and sequence confirmed), or blue lines (interaction found in literature). The thickness of the line indicates the strength of the interaction between two proteins. Dashed purple ellipses indicate shared interactors between IFT-B members.

FIGURE 2:. IFT-A and IFT-B gene expression in different adult tissues.

The heat map shows tissue-specific gene expression for IFT-A and IFT-B components (subcomplex IFT-B1 and IFT-B2) across differentiated human adult tissues. Raw transcript per million (TPM) values, representing gene expression values, were obtained from the GTEx database (https://www.gtexportal.org/home/). Red indicates higher expression (high TPM value) and blue indicates low expression (low TPM value), as reflected in the color gradient legend (right).