Rab11-FIP3 links the Rab11 GTPase and cytoplasmic dynein to mediate transport to the endosomal-recycling compartment

Horgan, Conor P.; Hanscom, Sara R.; Jolly, Rushee S.; Futter, Clare E.; McCaffrey, Mary W.

doi:10.1242/jcs.052670

Cited by 178 publications

(191 citation statements)

References 36 publications

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“…Rab11 was linked to cytoplasmic dynein via the direct interaction of Rab11-FIP3 with DLIC1 or DLIC2 [13,28]. On the basis of these previous studies, we questioned whether Dlic1 deficiency might impair ciliogenesis by blocking the transport of Rab11-mediated vesicle from the Golgi to cilia due to the reduced interaction between dynein and Rab11.…”

Section: Disrupted Rab11-vesicle Transport From the Golgi To The Basamentioning

confidence: 99%

“…Mutations in the gene encoding DLIC or depleting its gene product by RNAi were shown to result in a variety of mitotic defects from yeast to mammals [8][9][10][11]. DLIC1 also participates in intracellular vesicle transport via forming a complex with small GTPases Rab4 and Rab11, respectively [12,13]. However, the functions of the DLIC subunit in keeping the integrity of dynein and Golgi apparatus and the development of neurons are controversial.…”

Section: Introductionmentioning

confidence: 99%

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Dlic1 deficiency impairs ciliogenesis of photoreceptors by destabilizing dynein

Kong

Peng

et al. 2013

Cell Res

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Cytoplasmic dynein 1 is fundamentally important for transporting a variety of essential cargoes along microtubules within eukaryotic cells. However, in mammals, few mutants are available for studying the effects of defects in dynein-controlled processes in the context of the whole organism. Here, we deleted mouse Dlic1 gene encoding DLIC1, a subunit of the dynein complex. Dlic1 −/− mice are viable, but display severe photoreceptor degeneration. Ablation of Dlic1 results in ectopic accumulation of outer segment (OS) proteins, and impairs OS growth and ciliogenesis of photoreceptors by interfering with Rab11-vesicle trafficking and blocking efficient OS protein transport from Golgi to the basal body. Our studies show that Dlic1 deficiency partially blocks vesicle export from endoplasmic reticulum (ER), but seems not to affect vesicle transport from the ER to Golgi. Further mechanistic study reveals that lack of Dlic1 destabilizes dynein subunits and alters the normal subcellular distribution of dynein in photoreceptors, probably due to the impaired transport function of dynein. Our results demonstrate that Dlic1 plays important roles in ciliogenesis and protein transport to the OS, and is required for photoreceptor development and survival. The Dlic1 −/− mice also provide a new mouse model to study human retinal degeneration.

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Section: Disrupted Rab11-vesicle Transport From the Golgi To The Basamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dlic1 deficiency impairs ciliogenesis of photoreceptors by destabilizing dynein

Kong

Peng

et al. 2013

Cell Res

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“…Our current study reveals that a strong candidate to mediate this stimulation is the single fly BICD protein, which is known to be one of a small number of proteins recruited to the RNA element (Dix et al , 2013). It will be important to determine in the future whether other BICD family members such as BICDR proteins (Schlager et al , 2010) and unrelated cargo adaptors for dynein (Engelender et al , 1997; Horgan et al , 2010; van der Kant et al , 2013; van Spronsen et al , 2013) also regulate motor processivity by promoting the interaction with dynactin.…”

Section: Discussionmentioning

confidence: 99%

In vitro reconstitution of a highly processive recombinant human dynein complex

et al. 2014

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Cytoplasmic dynein is an approximately 1.4 MDa multi‐protein complex that transports many cellular cargoes towards the minus ends of microtubules. Several in vitro studies of mammalian dynein have suggested that individual motors are not robustly processive, raising questions about how dynein‐associated cargoes can move over long distances in cells. Here, we report the production of a fully recombinant human dynein complex from a single baculovirus in insect cells. Individual complexes very rarely show directional movement in vitro. However, addition of dynactin together with the N‐terminal region of the cargo adaptor BICD2 (BICD2N) gives rise to unidirectional dynein movement over remarkably long distances. Single‐molecule fluorescence microscopy provides evidence that BICD2N and dynactin stimulate processivity by regulating individual dynein complexes, rather than by promoting oligomerisation of the motor complex. Negative stain electron microscopy reveals the dynein–dynactin–BICD2N complex to be well ordered, with dynactin positioned approximately along the length of the dynein tail. Collectively, our results provide insight into a novel mechanism for coordinating cargo binding with long‐distance motor movement.

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“…The interaction of Rab29 with the minus-end microtubule motor dynein, which similar to other Rabs is likely to be indirect, 28,29 suggests a role for this GTPase in coupling TCRs internalized at the plasma membrane to the microtubules emanating from the centrosome. The fact that internalized TCRs accumulate in the Rab11 + pericentrosomal compartment in Rab29-depleted cells undergoing constitutive recycling indicates that Rab29 is dispensable for dynein-dependent trafficking of internalized TCRs to this compartment but is required for their subsequent movement to the centrosome where they can be coupled to kinesin for transport to the plasma membrane.…”

Section: Discussionmentioning

confidence: 97%

The small GTPase Rab29 is a common regulator of immune synapse assembly and ciliogenesis

et al. 2015

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Accumulating evidence underscores the T-cell immune synapse (IS) as a site of intense vesicular trafficking, on which productive signaling and cell activation crucially depend. Although the T-cell antigen receptor (TCR) is known to exploit recycling to accumulate to the IS, the specific pathway that controls this process remains to be elucidated. Here we demonstrate that the small GTPase Rab29 is centrally implicated in TCR trafficking and IS assembly. Rab29 colocalized and interacted with Rab8, Rab11 and IFT20, a component of the intraflagellar transport system that regulates ciliogenesis and participates in TCR recycling in the non-ciliated T cell, as assessed by co-immunoprecipitation and immunofluorescence analysis. Rab29 depletion resulted in the inability of TCRs to undergo recycling to the IS, thereby compromizing IS assembly. Under these conditions, recycling TCRs accumulated in Rab11 + endosomes that failed to polarize to the IS due to defective Rab29-dependent recruitment of the dynein microtubule motor. Remarkably, Rab29 participates in a similar pathway in ciliated cells to promote primary cilium growth and ciliary localization of Smoothened. These results provide a function for Rab29 as a regulator of receptor recycling and identify this GTPase as a shared participant in IS and primary cilium assembly. T-cell activation is triggered by T-cell antigen receptor (TCR) engagement by MHC-bound peptide dispayed by an antigen presenting cell (APC). While a substantial proportion of the TCR has long been known to be associated with recycling endosomes, 1 it is only recently that the central function of this pool has emerged with the finding that, on assembly of the specialized interface with the APC, known as the immune synapse (IS), intracellular TCRs are delivered to this location by polarized recycling. 2 This process ensures a steady supply of TCRs at the IS to sustain signaling for T-cell activation 3 and has been co-opted by other receptors, such as the transferrin receptor (TfR) and the chemokine receptor CXCR4, 4,5 as well as membrane-bound signaling mediators, such as the kinase Lck and the adaptor LAT. 6,7 Receptor recycling is orchestrated by the small GTPases Rab4 and Rab11. 8 Cargo specificity is achieved with the assistance of specific regulators and effectors. The TCR recycling pathway has only started to be delineated with the identification of specific mediators, which include Rab35 and its GAP EPI64C 9 and the actin adaptor WASH 10 . Specific combinations of Rabs and SNAREs have been recently associated with recycling endosomes carrying either Lck, or TCRζ and LAT. 11 We have moreover identified IFT20 12 and other components of the intraflagellar transport (IFT) system, which regulates ciliary assembly and function, 13 as unexpected regulators of TCR recycling in the non-ciliated T cell. 14 Recently a Rab GTPase subfamily, which includes Rab29, Rab32 and Rab38, has been implicated in trafficking of the Salmonella-containing vacuole (SCV) in infected epithelial cells. 15,16 Rab32 and Rab38 ...

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Rab11-FIP3 links the Rab11 GTPase and cytoplasmic dynein to mediate transport to the endosomal-recycling compartment

Cited by 178 publications

References 36 publications

Dlic1 deficiency impairs ciliogenesis of photoreceptors by destabilizing dynein

Dlic1 deficiency impairs ciliogenesis of photoreceptors by destabilizing dynein

In vitro reconstitution of a highly processive recombinant human dynein complex

The small GTPase Rab29 is a common regulator of immune synapse assembly and ciliogenesis

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