Specialized Cilia in Mammalian Sensory Systems

Abstract

Cilia and flagella are highly conserved and important microtubule-based organelles that project from the surface of eukaryotic cells and act as antennae to sense extracellular signals. Moreover, cilia have emerged as key players in numerous physiological, developmental, and sensory processes such as hearing, olfaction, and photoreception. Genetic defects in ciliary proteins responsible for cilia formation, maintenance, or function underlie a wide array of human diseases like deafness, anosmia, and retinal degeneration in sensory systems. Impairment of more than one sensory organ results in numerous syndromic ciliary disorders like the autosomal recessive genetic diseases Bardet-Biedl and Usher syndrome. Here we describe the structure and distinct functional roles of cilia in sensory organs like the inner ear, the olfactory epithelium, and the retina of the mouse. The spectrum of ciliary function in fundamental cellular processes highlights the importance of elucidating ciliopathy-related proteins in order to find novel potential therapies.

Glutamylation Regulates Transport, Specializes Function, and Sculpts the Structure of Cilia

“…Although virtually all cilia are built by a conserved intraflagellar transport (IFT) process and share a similar architecture, cilia and flagella adopt morphological specializations and serve diverse functions [1]. For example, the rods and cones of the retina are elaborately shaped cilia [2], while sperm have simple whip-like flagella that are variable in length and axoneme structure [3]. C. elegans amphid channel cilia, mammalian olfactory cilia, and mammalian renal primary cilia possess a proximal doublet region followed by a distal A-tubule singlet region [1, 2, 4, 5].…”

“…For example, the rods and cones of the retina are elaborately shaped cilia [2], while sperm have simple whip-like flagella that are variable in length and axoneme structure [3]. C. elegans amphid channel cilia, mammalian olfactory cilia, and mammalian renal primary cilia possess a proximal doublet region followed by a distal A-tubule singlet region [1, 2, 4, 5]. Another ciliary specialization is the ability to produce extracellular vesicles (EVs) called ectosomes [6–11].…”

Maturation arrest in early postnatal sensory receptors by deletion of the miR-183/96/182 cluster in mouse

“…Although highly specialized, similarities in embryonic origin underlie common features in their development (1). Following specification, lineage-restricted postmitotic precursors become structurally and functionally mature through a series of cellular differentiation events, collectively described as terminal differentiation (2). During maturation, sensory receptor cells typically develop microtubule-based primary cilia and in some cases actin-based membrane protrusions on apical membranes, which are sensory organelles, while maintaining apical basal polarity within sensory epithelia.…”

Primary Cilium-Mediated Crosstalk of Signaling Cascades in Ciliogenesis: Implications for Tumorigenesis and Senescence

“…1C). 4,5 Primary cilia lack motility because of the absence of the outer and inner dynein arms on the A tubule of the nine doublet MTs, a central pair of MTs, and radial spokes (Fig. 1C).…”

“…Two types of cilia are known in human beings: 9 + 2 or 9 + 0 MT-based axonemes, and both have been shown to be associated with various human diseases. [2][3][4] The 9 + 2 axonemes are subdivided into motile cilia (such as respiratory cilia or ependymal cilia) or nonmotile cilia (such as a kinocilium of hair cells of vertebrate inner ears). The 9 + 0 axonemes are subdivided into motile cilia (such as nodal cilia) or nonmotile cilia (primary cilia such as renal monocilia or photoreceptor-connecting cilia; Fig.…”