<i>Chlamydomonas IFT</i>88 and Its Mouse Homologue, Polycystic Kidney Disease Gene <i>Tg</i>737, Are Required for Assembly of Cilia and Flagella

TLDR

Intraflagellar transport (IFT) moves multi‑subunit protein particles along flagellar microtubules and is essential for flagellar assembly and maintenance, and the IFT88 subunit is conserved in mammals as Tg737, whose loss causes perinatal death from polycystic kidney disease. We cloned and sequenced a Chlamydomonas cDNA encoding the IFT88 subunit and identified an insertional mutant lacking this gene. The Chlamydomonas IFT88 mutant lacks flagella, and Tg737 mutant mice have shortened primary cilia, demonstrating that IFT is essential for cilia assembly and that its disruption can contribute to polycystic kidney disease.

Abstract

Intraflagellar transport (IFT) is a rapid movement of multi-subunit protein particles along flagellar microtubules and is required for assembly and maintenance of eukaryotic flagella. We cloned and sequenced a Chlamydomonas cDNA encoding the IFT88 subunit of the IFT particle and identified a Chlamydomonas insertional mutant that is missing this gene. The phenotype of this mutant is normal except for the complete absence of flagella. IFT88 is homologous to mouse and human genes called Tg737. Mice with defects in Tg737 die shortly after birth from polycystic kidney disease. We show that the primary cilia in the kidney of Tg737 mutant mice are shorter than normal. This indicates that IFT is important for primary cilia assembly in mammals. It is likely that primary cilia have an important function in the kidney and that defects in their assembly can lead to polycystic kidney disease.