Ciliary dysfunction in polycystic kidney disease: an emerging model with polarizing potential - PubMed (original) (raw)

Review

Ciliary dysfunction in polycystic kidney disease: an emerging model with polarizing potential

Robert J Kolb et al. Front Biosci. 2008.

Abstract

The majority of different cell types in the human body have a cilium, a thin rod-like structure of uniquely arranged microtubules that are encapsulated by the surface plasma membrane. The cilium originates from a basal body, a mature centriole that has migrated and docked to the cell surface. The non-motile cilia are microtubule-based organelles that are generally considered sensory structures. The purpose of this review is to discuss the practicality of the ciliary hypothesis as a unifying concept for polycystic kidney disease and to review current literature in the field of cilium biology, as it relates to mechanosensation and planar cell polarity. The polycystins and fibrocystin localization at the cilium and other subcellular localizations are discussed, followed by a hypothetical model for the cilium's role in mechanosensing, planar cell polarity, and cystogenesis.

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Figures

Figure 1

Figure 1

Mechanosensory protein complex. Among other subcellular localizations, it is thought that polycystin-1, polycystin-2 and fibrocystin form a mechanosensory complex protein in the cilium to sense fluid-shear stress. Polycystin-1 and polycystin-2 interact with each other at their COOH termini forming a polycystin complex. It is predicted that fibrocystin interacts with this complex through polycystin-2 via Kif as a possible adaptor protein.

Figure 2

Figure 2

Hypothetical model of cystogenesis. The illustration depicts mechanosensory function of renal tubular epithelial cilium. a. Each cilium plays an important role to transmit extracellular information, such as urine flow, into the cell. This message may provide critical signals to the cell regarding the direction of cell division along the tubule. b. Insults, such as genetic disorder or random mutation, will result in abnormal ciliary function to sense fluid movement. c. The functional abnormality in ciliary sensing may result in loss of planar cell polarity. d. Direction of cell division becomes randomized, resulting in increasing tubular diameter rather than tubular elongation. e. Budding of a cyst from the renal tubule and abnormal localizations of epidermal growth factor receptor (EGFR) and Na+/K+ ATPase pump are typical characteristics of the autosomal dominant polycystic kidney. f. The cyst is eventually enlarged and isolated. Multiple cysts from the neighboring nephrons are illustrated on the bottom left corner.

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