Motile and non-motile (primary) cilia are nearly ubiquitous cellular organelles. The dysfunction of cilia causes diseases known as ciliopathies. The number of reported ciliopathies (currently 35) is increasing, as is the number of established (187) and candidate (241) ciliopathy-associated genes. The characterization of ciliopathy-associated proteins and phenotypes has improved our knowledge of ciliary functions. In particular, investigating ciliopathies has helped us to understand the molecular mechanisms by which the cilium-associated basal body functions in early ciliogenesis, as well as how the transition zone functions in ciliary gating, and how intraflagellar transport enables cargo trafficking and signalling. Both basic biological and clinical studies are uncovering novel ciliopathies and the ciliary proteins involved. The assignment of these proteins to different ciliary structures, processes and ciliopathy subclasses (first order and second order) provides insights into how this versatile organelle is built, compartmentalized and functions in diverse ways that are essential for human health.

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Genes and molecular pathways underpinning ciliopathies

Proteomics of Primary Cilia by Proximity Labeling

The primary cilium is a hair-like surface-exposed organelle of the eukaryotic cell that decodes a variety of signals - such as odorants, light and Hedgehog morphogens - by altering the local concentrations and activities of signalling proteins. Signalling within the cilium is conveyed through a diverse array of second messengers, including conventional signalling molecules (such as cAMP) and some unusual intermediates (such as sterols). Diffusion barriers at the ciliary base establish the unique composition of this signalling compartment, and cilia adapt their proteome to signalling demands through regulated protein trafficking. Much progress has been made on the molecular understanding of regulated ciliary trafficking, which encompasses not only exchanges between the cilium and the rest of the cell but also the shedding of signalling factors into extracellular vesicles.

Establishing and regulating the composition of cilia for signal transduction.

Eukaryotic cilia and flagella are evolutionarily conserved organelles that protrude from the cell surface. The unique location and properties of cilia allow them to function in vital processes such as motility and signaling. Ciliary assembly and maintenance rely on intraflagellar transport (IFT), the bidirectional movement of a multicomponent transport system between the ciliary base and tip. Since its initial discovery more than two decades ago, considerable effort has been invested in dissecting the molecular mechanisms of IFT in a variety of model organisms. Importantly, IFT was shown to be essential for mammalian development, and defects in this process cause a number of human pathologies known as ciliopathies. Here, we review current knowledge of IFT with a particular emphasis on the IFT machinery and specific mechanisms of ciliary cargo recognition and transport.

/pdf/the-intraflagellar-transport-machinery-w34ua4yent.pdf

The Intraflagellar Transport Machinery

IFT–Cargo Interactions and Protein Transport in Cilia

https://www.cell.com/developmental-cell/pdf/S1534-5807(14)00590-5.pdf

Lee Js

Papers

The Intraflagellar Transport Protein IFT27 promotes BBSome exit from cilia through the GTPase ARL6/BBS3