Intraflagellar transport-A complex mediates ciliary entry and retrograde trafficking of ciliary G protein–coupled receptors

Abstract

The IFT-A complex is divided into core and peripheral subcomplexes composed of IFT122/IFT140/IFT144 and IFT43/IFT121/IFT139, respectively. IFT139-KO and IFT144-KO cell analyses show that IFT139 is dispensable for IFT-A assembly but essential for retrograde GPCR trafficking, whereas IFT144 is essential for IFT-A assembly and GPCR ciliary entry.

Practical method for targeted disruption of cilia-related genes by using CRISPR/Cas9-mediated, homology-independent knock-in system

“…It is noteworthy that all of the defects in ciliogenesis and/or ciliary protein trafficking observed in these KO cells can be restored by exogenous expression of corresponding proteins; the characterization of these KO cells has been reported in other studies (Funabashi et al. , 2017; Hirano et al. , 2017; Nozaki et al.…”

Intraflagellar transporter protein 140 (IFT140), a component of IFT‐A complex, is essential for male fertility and spermiogenesis in mice

“…3 4), which are typical phenotypes of retrograde trafficking deficiency (Hirano et al 2017; Iomini et al 2009; Tsao and Gorovsky 2008). This observation suggests IFT140 is involved in retrograde transport of flagellar components and is consistent with disruption of specific retrograde IFT proteins in Tetrahymena , Chlamydomonas and nematode (Blacque et al 2006; Iomini et al 2009; Tsao and Gorovsky 2008).…”

“…Mutations disrupting IFT subunits usually result in short or completely absent cilia/flagella, or formation of flagellar bulges due to defects in anterograde and/or retrograde transport (Absalon et al 2008; Iomini et al 2009; Tsao and Gorovsky 2008). In addition, knockdown of the IFT-A complex blocks access of Tubby-like protein 3 (TULP3) and G protein-coupled receptors into mammalian primary cilia (Hirano et al 2017; Mukhopadhyay et al 2010). …”

“…Mutations disrupting IFT subunits usually result in short or completely absent cilia/flagella, or formation of flagellar bulges due to defects in anterograde and/or retrograde transport (Absalon et al, 2008;Iomini, Li, Esparza, & Dutcher, 2009;Tsao & Gorovsky, 2008). In addition, knockdown of the IFT-A complex blocks access of Tubby-like protein 3 (TULP3) and G proteincoupled receptors into mammalian primary cilia (Hirano, Katoh, & Nakayama, 2017;Mukhopadhyay et al, 2010). IFT140 belongs to the complex IFT-A and is conserved in green algae, mice, flies, worms and humans (Behal et al, 2012;Crouse et al, 2014;Jensen et al, 2010;Xu et al, 2015).…”

Regulation of ciliary membrane protein trafficking and signalling by kinesin motor proteins

“…Fibrocystin and PC2 similarly require TULP3 for ciliary entrance , whereas ARL13B, SMO and ACIII do not . Similarly, the IFT‐A subunits IFT121 and IFT144 were shown to promote constitutive ciliary accumulation of a number of GPCRs , whereas IFT144 was implicated in constitutive ciliary entrance of GPR161 and signal‐dependent ciliary accumulation of SMO . Interestingly, the conserved C‐terminal tubby domain present in TULP3 and TUB not only associates with specific CTSs present in its ciliary cargo proteins but also binds strongly to phosphoinositide 4,5‐bisphosphate (PI(4,5)P2) .…”