Architecture and function of IFT complex proteins in ciliogenesis

Abstract

Cilia and flagella (interchangeable terms) are evolutionarily conserved organelles found on many different types of eukaryotic cells where they fulfill important functions in motility, sensory reception and signaling. The process of Intraflagellar Transport (IFT) is of central importance for both the assembly and maintenance of cilia, as it delivers building blocks from their site of synthesis in the cell body to the ciliary assembly site at the tip of the cilium. A key player in this process is the multi-subunit IFT-complex, which acts as an adapter between the motor proteins required for movement and the ciliary cargo proteins. Since the discovery of IFT more than 15 years ago, considerable effort has gone into the purification and characterization of the IFT complex proteins. Even though this has led to very interesting findings and has greatly improved our knowledge of the IFT process, we still know very little about the overall architecture of the IFT complex and the specific functions of the various subunits. In this review we will give an update on the knowledge of the structure and function of individual IFT proteins, and the way these proteins interact to form the complex that facilitates IFT.

Fig. 1

(a) Schematic representations of the primary structures of the 20 C. reinhardtii IFT proteins identified to date. Predicted secondary structure elements and domains/motifs identified using bioinformatics are indicated according to the legend. For IFT25, IFT27 and the N-terminal domain of IFT54, the available crystal and NMR structures where used to identify domains and derive the secondary structure. For subunits with no 3D structure determined, the secondary structure was predicted using the PSIPRED algorithm (Jones, 1999). Tetratricopeptide repeats (TPR) were predicted using the algorithms TPRpred (http://toolkit.tuebingen.mpg.de/tprpred) and REP (http://www.embl.de/andrade/papers/rep/search.html). The program REP was also used to predict WD40 repeats. Coiled coils were identified using COILS (Lupas et al., 1991; http://toolkit.tuebingen.mpg.de/pcoils) and Calponin-homology (CH) domains were identified using the HHPred algorithm (Soding et al., 2005; http://toolkit.tuebingen.mpg.de/hhpred) for IFT81 and IFT57. The CH domain of IFT54 was identified based on the determined NMR structure of this domain (PDB code 2EQO). (b) Simplified interaction map of IFT proteins and associated factors (see text for details). Direct interactions are indicated with solid lines and potential interactions with dashed lines. Abbreviation for the organisms in which the interactions have been reported are as follows: Cr, Chlamydomonas reinhardtii; Ce, Caenorhabditis elegans; Hs, Homo sapiens, Dr, Danio rerio; Mm, Mus musculus.