The Intraflagellar Transport Protein IFT20 Is Associated with the Golgi Complex and Is Required for Cilia Assembly

Follit, John A.; Tuft, Richard A.; Fogarty, Kevin E.; Pazour, Gregory J.

doi:10.1091/mbc.e06-02-0133

Cited by 455 publications

(606 citation statements)

References 57 publications

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“…(Scale bar: 2 mm.) (17,33), we attempted to identify the primary cilia, using immunohistochemistry, in control and Ift20:Wnt1-Cre embryos. In control embryos at E12.5, CNC-derived osteogenic cells, which were labeled with RUNX2, a key regulator of osteoblasts, had primary cilia ( Fig.…”

Section: Disruption Of Ift20 In Neural Crest Cells Results In Craniofmentioning

confidence: 99%

Canonical and noncanonical intraflagellar transport regulates craniofacial skeletal development

Noda¹,

Kitami²,

Kitami

et al. 2016

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

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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

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Section: Disruption Of Ift20 In Neural Crest Cells Results In Craniofmentioning

confidence: 99%

Canonical and noncanonical intraflagellar transport regulates craniofacial skeletal development

Noda¹,

Kitami²,

Kitami

et al. 2016

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

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“…Interestingly, localization of CYLD at the cilia tips is reminiscent of the enrichment observed for several other proteins such as EB1/EB3 (ref. 42), some IFT proteins 43 and, more recently, cep104/FAP256 (ref. 44).…”

Section: Discussionmentioning

confidence: 99%

The deubiquitinating enzyme CYLD controls apical docking of basal bodies in ciliated epithelial cells

et al. 2014

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CYLD is a tumour suppressor gene mutated in familial cylindromatosis, a genetic disorder leading to the development of skin appendage tumours. It encodes a deubiquitinating enzyme that removes Lys63-or linear-linked ubiquitin chains. CYLD was shown to regulate cell proliferation, cell survival and inflammatory responses, through various signalling pathways. Here we show that CYLD localizes at centrosomes and basal bodies via interaction with the centrosomal protein CAP350 and demonstrate that CYLD must be both at the centrosome and catalytically active to promote ciliogenesis independently of NF-kB. In transgenic mice engineered to mimic the smallest truncation found in cylindromatosis patients, CYLD interaction with CAP350 is lost disrupting CYLD centrosome localization, which results in cilia formation defects due to impairment of basal body migration and docking. These results point to an undiscovered regulation of ciliogenesis by Lys63 ubiquitination and provide new perspectives regarding CYLD function that should be considered in the context of cylindromatosis.

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“…In addition, two large complexes of 420 proteins called IFT A and IFT B are also essential for IFT, exemplified by mutations in IFT B, which lead to the absence of cilia or to shortened cilia, whereas defects in IFT A proteins lead to a bulged cilia. 18 Extraciliary functions of some of these subunits have been also described, [19][20][21] as for example, continuous shuttling of the protein IFT20 between the Golgi and the basal body, which facilitates the mobilization of specific cargo.…”

Section: Cilium: Structure and Signalingmentioning

confidence: 99%

Autophagy and regulation of cilia function and assembly

et al. 2014

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Motile and primary cilia (PC) are microtubule-based structures located at the cell surface of many cell types. Cilia govern cellular functions ranging from motility to integration of mechanical and chemical signaling from the environment. Recent studies highlight the interplay between cilia and autophagy, a conserved cellular process responsible for intracellular degradation. Signaling from the PC recruits the autophagic machinery to trigger autophagosome formation. Conversely, autophagy regulates ciliogenesis by controlling the levels of ciliary proteins. The cross talk between autophagy and ciliated structures is a novel aspect of cell biology with major implications in development, physiology and human pathologies related to defects in cilium function. Cell Death and Differentiation (2015) 22, 389-397; doi:10.1038/cdd.2014.171; published online 31 October 2014 FactsAutophagy is a degradative and recycling mechanism that allows cells to adapt to stress situations including nutrient deprivation. Primary cilia (PC) and motile cilia (MC) are sensory structures at the cell surface. PC sense nutrient, growth factor and calcium changes in the extracellular environment and also respond to mechanical stress. MC are beating structures that contribute to innate defense in the lung, for example. The PC is a site for the recruitment of autophagy-related (ATG) proteins that mediate autophagosome formation in response to cilium-dependent signaling. In turn, autophagy regulates the biogenesis of cilia by degrading certain proteins involved in cilia formation. Modulation of autophagy represents a new therapeutic opportunity in diseases related to defective cilia function. Open QuestionsHow are ATG proteins transported to the PC? How do ATG proteins recruited to the PC contribute to the biogenesis of phagophores and autophagosomes? Ciliary proteins are degraded by autophagy. How selective is this degradative pathway? Do some of these proteins contain motifs that result in selective engulfment by autophagosomes?What are the determinants that switch the degradation of ciliary proteins between basal and induced autophagy? Is there any specific function for cilium-dependent autophagy in ciliated cells? Do signals that trigger cilium-dependent autophagy depend on the stimuli (chemical, mechanical) or do all stimuli converge to a single signaling pathway upstream of the autophagy machinery? Can modulation of autophagy contribute to the restoration of cilium functions?Receptors, transporters and specialized plasma membrane structures such as cilia constitute the interfaces between the extracellular and intracellular milieu and allow the cells to trigger specific responses to adapt to changes imposed by the environment. Among these adaptive responses, macroautophagy (hereafter referred to as 'autophagy') is a catabolic process conserved in eukaryotic cells by which the cell recycles its own constituents. 1 Autophagy is involved in the adaptation to starvation, cell differentiation and development, the degradation of aberrant structure...

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The Intraflagellar Transport Protein IFT20 Is Associated with the Golgi Complex and Is Required for Cilia Assembly

Cited by 455 publications

References 57 publications

Canonical and noncanonical intraflagellar transport regulates craniofacial skeletal development

Canonical and noncanonical intraflagellar transport regulates craniofacial skeletal development

The deubiquitinating enzyme CYLD controls apical docking of basal bodies in ciliated epithelial cells

Autophagy and regulation of cilia function and assembly

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