Molecular basis underlying the ciliary defects caused by <i>IFT52</i> variations found in skeletal ciliopathies

Ishida, Yamato; Tasaki, Koshi; Katoh, Yohei; Nakayama, Kazuhisa

doi:10.1091/mbc.e22-05-0188

Cited by 5 publications

(6 citation statements)

References 51 publications

(228 reference statements)

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“…21 It is reported that the hetero-tetramer complex of IFT38, IFT52, IFT57 and IFT88 recruits the kinesin-II proteins (KIF3A/KIF3B/KAP3) to the IFT complex. 21,81 Of the four IFT proteins, IFT52 has the most important function in mediating the interaction with KIF3B of the kinesin-II complex. 21 However, many of the other IFT proteins perform additional functions to enhance the interaction of IFT-B with kinesin-II.…”

Section: Coordination Of Ift Complexes and Regulation Of Ciliary Tran...mentioning

confidence: 99%

“…The IFT complex consists of two multi-subunit subcomplexes, IFT-A and IFT-B. The formation of the IFT complex at the ciliary base is initiated by the spontaneous assembly of 16 different proteins (IFT20, 22,25,27,38,46,52,54,56,57,70,74,80,81,88 and 172) which form the complex structure of IFT-B. 17,18 Topologically, the IFT-B complex is divided into two subregions, referred to as the core (IFT-B1) and periphery (IFT-B2).…”

Section: Structural Features Of Ift52 In Context Of Ift-b Complexmentioning

confidence: 99%

“…The involvement of IFT52 in the anterograde transport of the IFT complex requires the activity of kinesin motor proteins 21 . It is reported that the hetero‐tetramer complex of IFT38, IFT52, IFT57 and IFT88 recruits the kinesin‐II proteins (KIF3A/KIF3B/KAP3) to the IFT complex 21,81 . Of the four IFT proteins, IFT52 has the most important function in mediating the interaction with KIF3B of the kinesin‐II complex 21 .…”

Section: Function Of Ift52 In Intraflagellar Transport and Signalingmentioning

confidence: 99%

“…By controlling the movement of cargoes, the IFT52 contributes to the maintenance of appropriate ciliary length 23 . Complete loss of IFT52 expression results in loss of cilia formation in cells, whereas suboptimal expression of IFT52 results in abnormal ciliary length 80–82 . The role of IFT52 in cilia biogenesis is multifaceted and includes its interactions with other IFT‐B proteins in maintenance of the stability of the IFT‐A/IFT‐B association 82 …”

Section: Function Of Ift52 In Intraflagellar Transport and Signalingmentioning

confidence: 99%

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The emerging functions of intraflagellar transport 52 in ciliary transport and ciliopathies

Udupa,

Ghosh

2024

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Ciliary transport in eukaryotic cells is an intricate and conserved process involving the coordinated assembly and functioning of a multiprotein intraflagellar transport (IFT) complex. Among the various IFT proteins, intraflagellar transport 52 (IFT52) plays a crucial role in ciliary transport and is implicated in various ciliopathies. IFT52 is a core component of the IFT‐B complex that facilitates movement of cargoes along the ciliary axoneme. Stable binding of the IFT‐B1 and IFT‐B2 subcomplexes by IFT52 in the IFT‐B complex regulates recycling of ciliary components and maintenance of ciliary functions such as signal transduction and molecular movement. Mutations in the IFT52 gene can disrupt ciliary trafficking, resulting in dysfunctional cilia and affecting cellular processes in ciliopathies. Such ciliopathies caused by IFT52 mutations exhibit a wide range of clinical features, including skeletal developmental abnormalities, retinal degeneration, respiratory failure and neurological abnormalities in affected individuals. Therefore, IFT52 serves as a promising biomarker for the diagnosis of various ciliopathies, including short‐rib thoracic dysplasia 16 with or without polydactyly. Here, we provide an overview of the IFT52‐mediated molecular mechanisms underlying ciliary transport and describe the IFT52 mutations that cause different disorders associated with cilia dysfunction.

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Section: Coordination Of Ift Complexes and Regulation Of Ciliary Tran...mentioning

confidence: 99%

Section: Structural Features Of Ift52 In Context Of Ift-b Complexmentioning

confidence: 99%

Section: Function Of Ift52 In Intraflagellar Transport and Signalingmentioning

confidence: 99%

Section: Function Of Ift52 In Intraflagellar Transport and Signalingmentioning

confidence: 99%

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The emerging functions of intraflagellar transport 52 in ciliary transport and ciliopathies

Udupa,

Ghosh

2024

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“… 14 Ift is driven by two molecular motors, involving cytoplasmic dynein2, which mediates transport from tip to base, and the heterotrimeric kinesin-2 complex comprised of Kif3a, Kif3b, and Kap3, which is responsible for transport from base to tip. 15 , 104 , 105 Mutations in the gene encoding the heavy chain of cytoplasmic dynein2 cause axoneme swelling because Ift-related proteins are trapped in cilia due to disruption of retrograde transport. 14 Gli cooperates with Kif3a and Kap3, where the interaction of Kap3 restricts Gli transcriptional activity.…”

Section: Hedgehog Signaling and The Primary Ciliummentioning

confidence: 99%

Hedgehog signaling in tissue homeostasis, cancers, and targeted therapies

Jing,

Wu,

Wang

et al. 2023

Sig Transduct Target Ther

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The past decade has seen significant advances in our understanding of Hedgehog (HH) signaling pathway in various biological events. HH signaling pathway exerts its biological effects through a complex signaling cascade involved with primary cilium. HH signaling pathway has important functions in embryonic development and tissue homeostasis. It plays a central role in the regulation of the proliferation and differentiation of adult stem cells. Importantly, it has become increasingly clear that HH signaling pathway is associated with increased cancer prevalence, malignant progression, poor prognosis and even increased mortality. Understanding the integrative nature of HH signaling pathway has opened up the potential for new therapeutic targets for cancer. A variety of drugs have been developed, including small molecule inhibitors, natural compounds, and long non-coding RNA (LncRNA), some of which are approved for clinical use. This review outlines recent discoveries of HH signaling in tissue homeostasis and cancer and discusses how these advances are paving the way for the development of new biologically based therapies for cancer. Furthermore, we address status quo and limitations of targeted therapies of HH signaling pathway. Insights from this review will help readers understand the function of HH signaling in homeostasis and cancer, as well as opportunities and challenges of therapeutic targets for cancer.

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