The Biology of Ciliary Dynamics (original) (raw)
Related papers
The photoreceptor cilium and its diseases
Current Opinion in Genetics & Development, 2019
Light sensation occurs in photoreceptor outer segments (OS), which derive from highly specialized primary cilia, based on structural and molecular similarities. Ciliary dysfunction causes ciliopathies, in which retinal degeneration is common. The connecting cilium (CC) is the obligate passage for proteins moving between ciliary and cellular compartment, controlling the correct distribution of proteins on either side of its barrier. While new mechanisms for selective entry of ciliary proteins are being elucidated, active transport out of the OS is increasingly studied. We further discuss other recent advances in the field, such as a role for the CC in docking and fusion of incoming transport vesicles, a newly proposed subcompartmentalization into proximal and distal CC, and mechanisms of OS membrane dynamics paralleling ectosome formation in other cilia.
Comprehensive Physiology, 2011
Cilia and flagella are surface-exposed, finger-like organelles whose core consists of a microtubule (MT)-based axoneme that grows from a modified centriole, the basal body. Cilia are found on the surface of many eukaryotic cells and play important roles in cell motility and in coordinating a variety of signaling pathways during growth, development, and tissue homeostasis. Defective cilia have been linked to a number of developmental disorders and diseases, collectively called ciliopathies. Cilia are dynamic organelles that assemble and disassemble in tight coordination with the cell cycle. In most cells, cilia are assembled during growth arrest in a multistep process involving interaction of vesicles with appendages present on the distal end of mature centrioles, and addition of tubulin and other building blocks to the distal tip of the basal body and growing axoneme; these building blocks are sorted through a region at the cilium base known as the ciliary necklace, and then transported via intraflagellar transport (IFT) along the axoneme toward the tip for assembly. After assembly, the cilium frequently continues to turn over and incorporate tubulin at its distal end in an IFT-dependent manner. Prior to cell division, the cilia are usually resorbed to liberate centrosomes for mitotic spindle pole formation. Here, we present an overview of the main cytoskeletal structures associated with cilia and centrioles with emphasis on the MTassociated appendages, fibers, and filaments at the cilium base and tip. The composition and possible functions of these structures are discussed in relation to cilia assembly, disassembly, and length regulation. C 2012 American Physiological Society.
Early steps in primary cilium assembly require EHD1/EHD3-dependent ciliary vesicle formation
Nature Cell Biology, 2015
Membrane association with mother centriole (M-centriole) distal appendages is critical for ciliogenesis initiation. How the Rab GTPase Rab11-Rab8 cascade functions in early ciliary membrane assembly is unknown. Here, we show that the membrane shaping proteins EHD1 and EHD3, in association with the Rab11-Rab8 cascade, function in early ciliogenesis. EHD1 and EHD3 localize to preciliary membranes and the ciliary pocket. EHD-dependent membrane tubulation is essential for ciliary vesicle formation from smaller distal appendage vesicles (DAVs). Importantly, this step functions in M-centriole to basal body transformation and recruitment of transition zone proteins and IFT20. SNAP29, a SNARE membrane fusion regulator and EHD1-binding protein, is also required for DAV-mediated ciliary vesicle assembly. Interestingly, only after ciliary vesicle assembly is Rab8 activated for ciliary growth. Our studies uncover molecular mechanisms informing a previously uncharacterized ciliogenesis step, whereby EHD1 and EHD3 reorganize the M-centriole and associated DAVs before coordinated ciliary membrane and axoneme growth.
The Ciliary Rootlet Maintains Long-Term Stability of Sensory Cilia
Molecular and Cellular Biology, 2005
The striated ciliary rootlet is a prominent cytoskeleton originating from basal bodies of ciliated cells. Although a familiar structure in cell biology, its function has remained unresolved. In this study, we carried out targeted disruption in mice of the gene for rootletin, a component of the rootlet. In the mutant, ciliated cells are devoid of rootlets. Phototransduction and ciliary beating in sensory and motile cilia initially exhibit no apparent functional deficits. However, photoreceptors degenerate over time, and mutant lungs appear prone to pathological changes consistent with insufficient mucociliary clearance. Further analyses revealed a striking fragility at the ciliary base in photoreceptors lacking rootlets. In vitro assays suggest that the rootlet is among the least dynamic of all cytoskeletons and interacts with actin filaments. Thus, a primary function of the rootlet is to provide structural support for the cilium. Inasmuch as photoreceptors elaborate an exceptionally enlarged sensory cilium, they are especially dependent on the rootlet for structural integrity and long-term survival.
EMBO reports, 2012
Both the basal body and the microtubule-based axoneme it nucleates have evolutionarily conserved subdomains crucial for cilium bio genesis, function and maintenance. Here, we focus on two conspicuous but underappreciated regions of these structures that make membrane connections. One is the basal body distal end, which includes transition fibres of largely undefined composition that link to the base of the ciliary membrane. Transition fibres seem to serve as docking sites for intraflagellar transport particles, which move proteins within the ciliary compartment and are required for cilium biogenesis and sustained function. The other is the proximal-most region of the axoneme, termed the transition zone, which is characterized by Y-shaped linkers that span from the axoneme to the ciliary necklace on the membrane surface. The transition zone comprises a growing number of cilio pathy proteins that function as modular components of a ciliary gate. This gate, which forms early during ciliogenesis, might function in part by regulating intraflagellar transport. Together with a recently described septin ring diffusion barrier at the ciliary base, the transition fibres and transition zone deserve attention for their varied roles in forming functional ciliary compartments.
The dynamic cilium in human diseases
PathoGenetics, 2009
Cilia are specialized organelles protruding from the cell surface of almost all mammalian cells. They consist of a basal body, composed of two centrioles, and a protruding body, named the axoneme. Although the basic structure of all cilia is the same, numerous differences emerge in different cell types, suggesting diverse functions. In recent years many studies have elucidated the function of 9+0 primary cilia. The primary cilium acts as an antenna for the cell, and several important pathways such as Hedgehog, Wnt and planar cell polarity (PCP) are transduced through it. Many studies on animal models have revealed that during embryogenesis the primary cilium has an essential role in defining the correct patterning of the body. Cilia are composed of hundreds of proteins and the impairment or dysfunction of one protein alone can cause complete loss of cilia or the formation of abnormal cilia. Mutations in ciliary proteins cause ciliopathies which can affect many organs at different levels of severity and are characterized by a wide spectrum of phenotypes. Ciliary proteins can be mutated in more than one ciliopathy, suggesting an interaction between proteins. To date, little is known about the role of primary cilia in adult life and it is tempting to speculate about their role in the maintenance of adult organs. The state of the art in primary cilia studies reveals a very intricate role. Analysis of cilia-related pathways and of the different clinical phenotypes of ciliopathies helps to shed light on the function of these sophisticated organelles. The aim of this review is to evaluate the recent advances in cilia function and the molecular mechanisms at the basis of their activity.
The ciliary pocket: a once-forgotten membrane domain at the base of cilia
Biology of the Cell, 2011
The PC (primary cilium) is present on most cell types in both developing and adult tissues in vertebrates. Despite multiple reports in the 1960s, the PC was almost forgotten for decades by most of the cell biology community, mainly because its function appeared enigmatic. This situation changed 10 years ago with the key discovery that this fascinating structure is the missing link between complex genetic diseases and key signalling pathways during development and tissue homoeostasis. A similar misfortune might have happened to an original membrane domain found at the base of PC in most cell types and recently termed the 'ciliary pocket'. A morphologically related structure has also been described at the connecting cilium of photoreceptors and at the flagellum in spermatids. Its organization is also reminiscent of the flagellar pocket, a plasma membrane invagination specialized in uptake and secretion encountered in kinetoplastid protozoa. The exact function of the ciliary pocket remains to be established, but the recent observation of endocytic activity coupled to the fact that vesicular trafficking plays important roles during ciliogenesis brought excitement in the ciliary community. Here, we have tried to decipher what this highly conserved membrane domain could tell us about the function and/or biogenesis of the associated cilium. 3 To whom correspondence should be addressed (email alexandre.benmerah@inserm.fr).
Development Growth & Differentiation, 2017
Besides the role to generate a fluid flow in the surrounding medium, eukaryotic cilia have a crucial function in sensing external signals such as chemical or mechanical stimuli. A large body of work has shown that cilia are frequently found in various types of sensory cells and are closely related to many regulatory mechanisms in differentiation and development. However, we do not yet have a definitive answer to the fundamental question, "why cilia?" It has been a long-standing mystery why cells use cilia for sensing external signals. To shed light on this, we sought to describe the kinetics of signaling with theoretical approaches. Based on the results, here we propose a new role of cilia as a cell-signaling enhancer. The enhancing effect comes from restricted volume for the free intra-ciliary diffusion of molecules due to the cylindrical shape of cilia, which can facilitate quick accumulation of intracellular signaling molecules. Our simulations demonstrate that both the rate and amplitude of response in signal transduction depend on where the membrane receptors or channels are located along the ciliary shaft. In addition, the calculated transfer function of cilia regarded as a transmitter of external signals also suggests the properties of cilia as a signal enhancer. Since such unique composition of receptors and channels in cilia is found in various types of eukaryotic cells, signal enhancing is presumably one of the most essential and conserved roles of cilia.