CILIA: before and after

Abstract

This is a history of cilia research before and after the discovery of intraflagellar transport (IFT) and the link between primary cilia ciliogenesis and polycystic kidney disease (PKD). Before IFT, ca. the beginning of the new millennium, although sensory and primary cilia were well described, research was largely focused on motile cilia, their structure, movement, and biogenesis. After IFT and the link to PKD, although work on motile cilia has continued to progress, research on primary cilia has exploded, leading to new insights into the role of cilia in cell signaling and development. Genomics, proteomics, and new imaging techniques have unified the field and pointed out the critical role of cilia as a restricted cell organellar compartment, functionally integrated with other cell organelles including the autophagosome and the nucleus.

Keywords: Autophagy; Ciliary motility; Ciliogenesis; Ciliopathies; Intraflagellar transport (IFT); Nucleoporin; Primary cilia; Transition zone.

Fig. 1

Current models of protein localization in the transition zone. a Localization based on aligned superresolution images of multiple single-colored STED images and an EM image of a RPE-1 cell primary cilium. TMEM67 and TCTN2 lie at the ciliary membrane in the ciliary necklace region. MSK1 is in the area of the ciliary pores (Y-links), while RPGRIP1L is at the same level but more proximal to the axonemal MTs; CEP290 is at the base of the zone. With permission from [79], courtesy of Jung-Chi Laio. b The position of the B9D1 complex proteins in relation to other transition zone proteins. In IMCD cells growing primary cilia, TCTN, TMEM 231, and TMEM17 lie in positions to be part of the ciliary necklace. An MSK1, B9D1-2 complex is anchored to the ciliary membrane at the level of the ciliary pores, and the stem of the Y-link is formed by CC2D2A resting on Jouberin (AHI-1). The positions of CEP290 and RPGRIP1L are not specified. With permission from [81], courtesy of Andrew S. Peterson. c Protein localization in the transition zone of C. elegans based on video reconstruction using mutant phenotypes. CEP-290 is a component of the apical ring, a central cylinder internal to the axonemal MTs and MKS and NPHP modules form the ciliary pores/Y-links. With permission from [82], courtesy of Alexander Dammermann. d A second model of the C. elegans transition zone based on protein localization, FRAP, and superresolution microscopy. RPGRIP1L and TMEM67 lie at the base of the zone forming a ring extending from the axoneme to the membrane. Distally MKS and NPHP proteins form rings or spirals whose periodicity and immobility correspond to the Y-links and ciliary necklace. From [83], courtesy of Oliver E. Blacque