Ciliopathies: the trafficking connection - PubMed (original) (raw)

Review

. 2014 Oct;15(10):1031-56.

doi: 10.1111/tra.12195. Epub 2014 Aug 11.

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Review

Ciliopathies: the trafficking connection

Kayalvizhi Madhivanan et al. Traffic. 2014 Oct.

Abstract

The primary cilium (PC) is a very dynamic hair-like membrane structure that assembles/disassembles in a cell-cycle-dependent manner and is present in almost every cell type. Despite being continuous with the plasma membrane, a diffusion barrier located at the ciliary base confers the PC properties of a separate organelle with very specific characteristics and membrane composition. Therefore, vesicle trafficking is the major process by which components are acquired for cilium formation and maintenance. In fact, a system of specific sorting signals controls the right of cargo admission into the cilia. Disruption to the ciliary structure or its function leads to multiorgan diseases known as ciliopathies. These illnesses arise from a spectrum of mutations in any of the more than 50 loci linked to these conditions. Therefore, it is not surprising that symptom variability (specific manifestations and severity) among and within ciliopathies appears to be an emerging characteristic. Nevertheless, one can speculate that mutations occurring in genes whose products contribute to the overall vesicle trafficking to the PC (i.e. affecting cilia assembly) will lead to more severe symptoms, whereas those involved in the transport of specific cargoes will result in milder phenotypes. In this review, we summarize the trafficking mechanisms to the cilia and also provide a description of the trafficking defects observed in some ciliopathies which can be correlated to the severity of the pathology.

Keywords: ciliopathies; endocytic pathway; primary cilia; secretory pathway; vesicle trafficking.

© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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Figures

Figure 1

Figure 1. The PC is an isolated domain

(A) The barrier at the ciliary base gives the ciliary membrane its unique identity in terms of lipid and protein composition (see text for details). (B) Cross-sections bottom up of the ciliary base depicting the proximal transition fibres (I), Septin ring and the ciliary pore complex (II) and the distal Y-links (III) (See text for details).

Figure 2

Figure 2. Pathways for transport of material to the base of the cilia

Secretory pathway (I) Endocytic-recycling pathway (II) Dynein-Dynactin complexes (III). (See text for details)

Figure 3

Figure 3. Transport of Material across and within the cilia

Movement across the cilia mediated by the BBSome and activated Ran gradient system. Co-ordination of IFT inside the cilia by the BBSome for anterograde and retrograde trafficking (See text for details).

Figure 4

Figure 4

A Graphical Representation of the overlap of genes involved in ciliopathies.

Figure 5

Figure 5. Ciliary trafficking defects in ciliopathies

(A) Normal Cilia. (B) NPHP and BBS: no ciliogenesis defect, specific ciliary cargo trafficking defect. (C) LS and JBTS: ciliogenesis affected due to defective material delivery for ciliary construction. (D) MKS: TZ components missing resulting in the loss of ciliary boundary

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