Cilia in the CNS: the quiet organelle claims center stage - PubMed (original) (raw)

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Cilia in the CNS: the quiet organelle claims center stage

Angeliki Louvi et al. Neuron. 2011.

Abstract

The primary cilium is a cellular organelle that is almost ubiquitous in eukaryotes, yet its functions in vertebrates have been slow to emerge. The last fifteen years have been marked by accelerating insight into the biology of primary cilia, arising from the synergy of three major lines of research. These research programs describe a specialized mode of protein trafficking in cilia, reveal that genetic disruptions of primary cilia cause complex human disease syndromes, and establish that Sonic hedgehog (Shh) signal transduction requires the primary cilium. New lines of research have branched off to investigate the role of primary cilia in neuronal signaling, adult neurogenesis, and brain tumor formation. We review a fast expanding literature to determine what we now know about the primary cilium in the developing and adult CNS and what new directions should lead to further clarity.

Copyright © 2011 Elsevier Inc. All rights reserved.

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Figures

Figure 1

Figure 1. The structure of a primary cilium

(A) Major components are the ciliary axoneme, composed of microtubules (green), the ciliary membrane (purple) and the basal body (blue), which is a modified mother centriole. Modifications of the basal body include transition fibers (orange) that form a permeable barrier between the cilium and the rest of the cell, the basal foot and cap (pink) and striated rootlets (black horizontal lines), which provide mechanical support (Seeley and Nachury, 2010). A cross-section through the axoneme shows nine paired microtubules (the 9+0 configuration). (B) Macromolecules (sun shapes) important for ciliogenesis attach to IFT particles and travel along microtubules towards the ciliary tip using a kinesin motor. Turnover products (stars) are carried back to the ciliary base by IFT particles attached to a dynein motor. (C) Electronmicrograph of a primary cilium in an adult mouse brain. Visible features schematized in (A) include the axoneme, basal body, a transition fiber (tf), the basal foot and cap (bfc) and the daughter centriole (dc), which lies close to the basal body. Arrowheads indicate possible IFT particles travelling along the cilium. Scale bar in C is 0.5 microns.

Figure 2

Figure 2. The structure of secondary and specialized sensory cilia

(A) Secondary cilia structurally resemble primary cilia, except that the axonemes of secondary cilia display a 9+2 microtubule configuration. The outer nine paired microtubules are attached to outer and inner dynein arms and connected to the central pair of tubules by radial spokes; this allows the secondary cilium self-generated motility. In the CNS, multiplesecondary cilia on ependymal cells lining the ventricles regulate the flow of cerebrospinal fluid (see text). (B) A ciliary segment joins the outer and inner segments (OS and IS) of the retinal photoreceptor and has the 9+0 configuration of a primary cilium. (C) Olfactory receptor neurons (ORNs) have cilia with a hybrid character. The cilia at the dendritic tips of each ORN display the 9+2 microtubule configuration, but lack the dynein machinery needed to generate motion (Arstila and Wersall, 1967; Jenkins et al., 2009). ORN cilia sample odorants in the mucus layer (yellow) at the surface of the olfactory epithelium (orange). ORN axons project to the olfactory bulb (OB).

Figure 3

Figure 3. The cilium as a sensory transduction organelle

At left an ORN extends a dendrite ending in a cluster of cilia (purple). To the right, signal transduction in an ORN cilium. An odorant (red ball) binds to the olfactory receptor (R), coupled to the G-protein Golf. Activation of ACIII increases cAMP. cAMP opens CNG ion channels, causing an influx of Ca++ (green) and Na+ (red) ions which depolarizes the ORN. Raised Ca++ levels open Cl− (blue) channels, allowing an efflux of Cl−, further depolarizing the cell, and amplifying the odorant signal. The depolarized potential of the cilium spreads passively to the somatic membrane of the ORN where it activates Ca++, Na+ and K- channels, leading to the firing of an action potential.

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