Transport and barrier mechanisms that regulate ciliary compartmentalization and ciliopathies

Nat Rev Nephrol. 2024 Feb;20(2):83-100. doi: 10.1038/s41581-023-00773-2. Epub 2023 Oct 23.

Abstract

Primary cilia act as cell surface antennae, coordinating cellular responses to sensory inputs and signalling molecules that regulate developmental and homeostatic pathways. Cilia are therefore critical to physiological processes, and defects in ciliary components are associated with a large group of inherited pleiotropic disorders - known collectively as ciliopathies - that have a broad spectrum of phenotypes and affect many or most tissues, including the kidney. A central feature of the cilium is its compartmentalized structure, which imparts its unique molecular composition and signalling environment despite its membrane and cytosol being contiguous with those of the cell. Such compartmentalization is achieved via active transport pathways that bring protein cargoes to and from the cilium, as well as gating pathways at the ciliary base that establish diffusion barriers to protein exchange into and out of the organelle. Many ciliopathy-linked proteins, including those involved in kidney development and homeostasis, are components of the compartmentalizing machinery. New insights into the major compartmentalizing pathways at the cilium, namely, ciliary gating, intraflagellar transport, lipidated protein flagellar transport and ciliary extracellular vesicle release pathways, have improved our understanding of the mechanisms that underpin ciliary disease and associated renal disorders.

Publication types

  • Review

MeSH terms

  • Biological Transport
  • Cell Membrane / metabolism
  • Cilia / metabolism
  • Ciliopathies* / metabolism
  • Humans
  • Protein Transport