Primary cilia-associated protein IFT172 in ciliopathies

Abstract

Cilium is a highly conserved antenna-like structure protruding from the surface of the cell membrane, which is widely distributed on most mammalian cells. Two types of cilia have been described so far which include motile cilia and immotile cilia and the latter are also known as primary cilia. Dysfunctional primary cilia are commonly associated with a variety of congenital diseases called ciliopathies with multifaceted presentations such as retinopathy, congenital kidney disease, intellectual disability, cancer, polycystic kidney, obesity, Bardet Biedl syndrome (BBS), etc. Intraflagellar transport (IFT) is a bi-directional transportation process that helps maintain a balanced flow of proteins or signaling molecules essential for the communication between cilia and cytoplasm. Disrupted IFT contributes to the abnormal structure or function of cilia and frequently promotes the occurrence of ciliopathies. Intraflagellar transport 172 (IFT172) is a newly identified member of IFT proteins closely involved in some rare ciliopathies such as Mainzer-Saldino syndrome (MZSDS) and BBS, though the underpinning causal mechanisms remain largely elusive. In this review, we summarize the key findings on the genetic and protein characteristic of IFT172, as well as its function in intraflagellar transport, to provide comprehensive insights to understand IFT172-related ciliopathies.

Keywords: IFT172; bardet biedl syndrome; ciliopathy; intraflagellar transport; primary cilia.

FIGURE 1

Primary cilium anchors within cytoplasm via basal bodies and extends like an “antenna” from a cell surface. Doublet microtubules growing from basal bodies form the backbone of the primary cilium, along which cargos are transported on IFT driven by kinesin and dynein proteins. The IFT complexes are assembled at the ciliary base, then move along the ciliary axoneme using the IFT-B machinery to reach the ciliary tip, where they reorganize for retrograde transport to form the IFT-A. Arrows indicate the direction of cargo flow.

FIGURE 2

Characterization of the Chlamydomonas IFT172 gene and its protein. (A) The Chlamydomonas IFT172 gene has 15 exons and 14 introns, the length in bp is listed for each of the introns. (B) The domain architecture of IFT172 from Chlamydomonas. IFT172 contains seven WD repeats and seven WAA repeats. (C) Schematic representation of the conformational transformation of monomeric IFT172.