Immune synapse targeting of specific recycling receptors by the intraflagellar transport system

Finetti, Francesca; Patrussi, Laura; Masi, Giulia; Onnis, Anna; Galgano, Donatella; Lucherini, Orso Maria; Pazour, Gregory J.; Baldari, Cosima T.

doi:10.1242/jcs.139337

Cited by 96 publications

(144 citation statements)

References 57 publications

Supporting

Mentioning

133

Contrasting

Unclassified

Order By: Relevance

“…S8). The KPL-IFF model may implicitly be capturing TCR surface dynamics because directed movement (47) combined with polarized recycling (48,49) of TCR into the immune synapse may balance with TCR internalization (46) to maintain the relatively constant TCR concentration at the immune synapse assumed by the KPL-IFF model, which is consistent with previous calculations (50). A recent study has shown that changing the pMHC affinity can induce a program that over a timescale of several days changes TCR levels (51).…”

Section: Fig 4 Systematic Analyses Of Signaling Models Reveals Thatmentioning

confidence: 99%

Architecture of a minimal signaling pathway explains the T-cell response to a 1 million-fold variation in antigen affinity and dose

Lever

Lim

Krüger

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

141

View full text Add to dashboard Cite

T cells must respond differently to antigens of varying affinity presented at different doses. Previous attempts to map peptide MHC (pMHC) affinity onto T-cell responses have produced inconsistent patterns of responses, preventing formulations of canonical models of T-cell signaling. Here, a systematic analysis of T-cell responses to 1 million-fold variations in both pMHC affinity and dose produced bell-shaped dose–response curves and different optimal pMHC affinities at different pMHC doses. Using sequential model rejection/identification algorithms, we identified a unique, minimal model of cellular signaling incorporating kinetic proofreading with limited signaling coupled to an incoherent feed-forward loop (KPL-IFF) that reproduces these observations. We show that the KPL-IFF model correctly predicts the T-cell response to antigen copresentation. Our work offers a general approach for studying cellular signaling that does not require full details of biochemical pathways.

show abstract

Section: Fig 4 Systematic Analyses Of Signaling Models Reveals Thatmentioning

confidence: 99%

Architecture of a minimal signaling pathway explains the T-cell response to a 1 million-fold variation in antigen affinity and dose

Lever

Lim

Krüger

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

141

View full text Add to dashboard Cite

show abstract

“…This finding raises the possibility that IFT20 might participate in intracellular membrane trafficking, in addition to its role in ciliary assembly. Supporting this hypothesis, recent studies have demonstrated that IFT20 is associated with the trafficking of ciliary membrane proteins from the Golgi to the cilium, opsin trafficking, and membrane trafficking in lymphoid and myeloid cells (18,19,33,48); however, it remains unclear whether IFT20 functions as a noncanonical IFT system during craniofacial skeletal development. Ift20:Wnt1-Cre embryos showed immature bone mineralization (Fig.…”

Section: Ift20 Is Critical For Regulating the Trafficking Of Procollamentioning

confidence: 99%

“…Supporting this idea, the deletion of Ift20 in mouse kidney causes a lack of primary cilia and leads to polycystic kidney disease (17). In addition to the traditional role of IFT in cilium assembly, recent studies have found that an IFT-like particle organized by IFT20 is recruited to the immune synapse for T-cell receptor recycling (18,19). These studies suggest that IFT proteins participate in intracellular membrane trafficking in immune cells; however, it remains unclear how IFT20 governs developmental processes, including skeletal formation, and how it functions in other cell types, such as multipotent stem cells.…”

mentioning

confidence: 98%

Canonical and noncanonical intraflagellar transport regulates craniofacial skeletal development

Noda¹,

Kitami²,

Kitami

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The primary cilium is a cellular organelle that coordinates signaling pathways critical for cell proliferation, differentiation, survival, and homeostasis. Intraflagellar transport (IFT) plays a pivotal role in assembling primary cilia. Disruption and/or dysfunction of IFT components can cause multiple diseases, including skeletal dysplasia. However, the mechanism by which IFT regulates skeletogenesis remains elusive. Here, we show that a neural crest-specific deletion of intraflagellar transport 20 (Ift20) in mice compromises ciliogenesis and intracellular transport of collagen, which leads to osteopenia in the facial region. Whereas platelet-derived growth factor receptor alpha (PDGFRα) was present on the surface of primary cilia in wildtype osteoblasts, disruption of Ift20 down-regulated PDGFRα production, which caused suppression of PDGF-Akt signaling, resulting in decreased osteogenic proliferation and increased cell death. Although osteogenic differentiation in cranial neural crest (CNC)-derived cells occurred normally in Ift20-mutant cells, the process of mineralization was severely attenuated due to delayed secretion of type I collagen. In control osteoblasts, procollagen was easily transported from the endoplasmic reticulum (ER) to the Golgi apparatus. By contrast, despite having similar levels of collagen type 1 alpha 1 (Col1a1) expression, Ift20 mutants did not secrete procollagen because of dysfunctional ER-to-Golgi trafficking. These data suggest that in the multipotent stem cells of CNCs, IFT20 is indispensable for regulating not only ciliogenesis but also collagen intracellular trafficking. Our study introduces a unique perspective on the canonical and noncanonical functions of IFT20 in craniofacial skeletal development.cranial neural crest cells | intracellular trafficking | intraflagellar transport | PDGF signaling | primary cilia

show abstract

“…We have recently shown that IFT20 colocalizes in part with Rab11 in T-cells (Finetti et al, 2014), raising the possibility that IFT20 and Rab8 might associate at Rab11 + endosomes. Immunofluorescence analysis showed indeed a significant colocalization of IFT20 with Rab8 (Fig.…”

Section: Rab8 Colocalizes With Rab11 and Ift20 At A Pericentrosomal Cmentioning

confidence: 99%

“…Moreover the TCR can be found in endosomes marked by Rab35 and its GAP EPI64C (Patino-Lopez et al, 2008). We have recently demonstrated that IFT20, a component of the intraflagellar transport (IFT) system that is responsible for the assembly and maintenance of cilia and flagella (Pazour and Bloodgood, 2008;Pedersen and Rosenbaum, 2008), is a central regulator of the pathway that regulates TCR recycling (Finetti et al, 2009), interacting with Rab5 to promote TCR trafficking from early endosomes (Finetti et al, 2014).…”

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

Journal of Cell Science

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Immune synapse targeting of specific recycling receptors by the intraflagellar transport system

Cited by 96 publications

References 57 publications

Architecture of a minimal signaling pathway explains the T-cell response to a 1 million-fold variation in antigen affinity and dose

Architecture of a minimal signaling pathway explains the T-cell response to a 1 million-fold variation in antigen affinity and dose

Canonical and noncanonical intraflagellar transport regulates craniofacial skeletal development

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

Contact Info

Product

Resources

About