The Intraflagellar Transport Protein IFT27 promotes BBSome exit from cilia through the GTPase ARL6/BBS3

102

The assembly and maintenance of most cilia and flagella rely on intraflagellar transport (IFT). Recent in vitro studies have suggested that, together, the calponin-homology domain within the IFT81 N-terminus and the highly basic N-terminus of IFT74 form a module for IFT of tubulin. By using Chlamydomonas mutants for IFT81 and IFT74, we tested this hypothesis in vivo. Modification of the predicted tubulin-binding residues in IFT81 did not significantly affect basic anterograde IFT and length of steady-state flagella but slowed down flagellar regeneration, a phenotype similar to that seen in a strain that lacks the IFT74 N-terminus. In both mutants, the frequency of tubulin transport by IFT was greatly reduced. A double mutant that combined the modifications to IFT81 and IFT74 was able to form only very short flagella. These results indicate that, together, the IFT81 and IFT74 N-termini are crucial for flagellar assembly, and are likely to function as the main module for IFT of tubulin.

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Together, the IFT81 and IFT74 N-termini form the main module for intraflagellar transport of tubulin

Kubo

Brown

Bellvé

et al. 2016

102

“…For example, in contrast to IFT88, IFT81 and IFT74 serve as a ʻtubulin module' that binds and transports tubulin within cilia (Bhogaraju et al, 2013). IFT25 (HSPB11) and IFT27 act as an ʻShh module' and are important in localizing Shh signaling components within cilia (Eguether et al, 2014;Keady et al, 2012;Liew et al, 2014). Similar to IFT88, we observed pooling of IFT81 at the Ift56 hop ciliary base.…”

Section: Ift56 Is Required For Integrity Of the Iftb Complex In Ciliamentioning

confidence: 73%

“…This defect in Gli2 accumulation is likely to be due to the strong reduction in ciliary IFT27. Recent evidence suggests that IFT27/25 promotes transport of ciliary Smo and Ptch1 through a BBSome-dependent mechanism (Eguether et al, 2014;Keady et al, 2012;Liew et al, 2014). However, there is little evidence of whether or how Gli might be transported by IFT proteins.…”

Section: Discussionmentioning

confidence: 99%

IFT56 regulates vertebrate developmental patterning by maintaining IFTB complex integrity and ciliary microtubule architecture

Xin¹,

Christopher²,

Zeng³

et al. 2017

Cilia are key regulators of animal development and depend on intraflagellar transport (IFT) proteins for their formation and function, yet the roles of individual IFT proteins remain unclear. We examined the Ift56 hop mouse mutant and reveal novel insight into the function of IFT56, a poorly understood IFTB protein. Ift56 hop mice have normal cilia distribution but display defective cilia structure, including abnormal positioning and number of ciliary microtubule doublets. We show that Ift56 hop cilia are unable to accumulate Gli proteins efficiently, resulting in developmental patterning defects in Shh signaling-dependent tissues such as the limb and neural tube. Strikingly, core IFTB proteins are unable to accumulate normally within Ift56 hop cilia, including IFT88, IFT81 and IFT27, which are crucial for key processes such as tubulin transport and Shh signaling. IFT56 is required specifically for the IFTB complex, as IFTA components and proteins that rely on IFTA function are unaffected in Ift56 hop cilia. These studies define a distinct and novel role for IFT56 in IFTB complex integrity that is crucial for cilia structure and function and, ultimately, animal development.

“…Moreover, Rab8 participates in recycling of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors to the dendritic spine surface as well as in the intracellular transport of the metabotropic glutamate receptor type 1 in neuronal cells (Esseltine et al, 2012;Gerges et al, 2004). Rab8 is activated at the base of the cilium by its guanine nucleotide exchanger Rabin8 (also known as RAB3IP), where it is recruited by the BBSome, a multimolecular complex that cooperates with the IFT system in the ciliary trafficking of membrane proteins (Liew et al, 2014;Nachury et al, 2007;Wei et al, 2012). A functional link between Rab8 and the recycling compartment in ciliated cells has been established with the finding that Rabin8 interacts with GTP-bound Rab11 and is carried to pericentrosomal Rab8 by Rab11 + vesicles, in association with the TRAPPII complex (Westlake et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

The small GTPase Rab8 interacts with VAMP-3 to regulate the delivery of recycling TCRs to the immune synapse

Finetti

Patrussi

Galgano

et al. 2015

IFT20, a component of the intraflagellar transport (IFT) system that controls ciliogenesis, regulates immune synapse assembly in the non-ciliated T-cell by promoting T-cell receptor (TCR) recycling. Here, we have addressed the role of Rab8 (for which there are two isoforms Rab8a and Rab8b), a small GTPase implicated in ciliogenesis, in TCR traffic to the immune synapse. We show that Rab8, which colocalizes with IFT20 in Rab11 + endosomes, is required for TCR recycling. Interestingly, as opposed to in IFT20-deficient T-cells, TCR + endosomes polarized normally beneath the immune synapse membrane in the presence of dominant-negative Rab8, but were unable to undergo the final docking or fusion step. This could be accounted for by the inability of the vesicular (v)-SNARE VAMP-3 to cluster at the immune synapse in the absence of functional Rab8, which is responsible for its recruitment. Of note, and similar to in T-cells, VAMP-3 interacts with Rab8 at the base of the cilium in NIH-3T3 cells, where it regulates ciliary growth and targeting of the protein smoothened. The results identify Rab8 as a new player in vesicular traffic to the immune synapse and provide insight into the pathways co-opted by different cell types for immune synapse assembly and ciliogenesis.