Ndel1 suppresses ciliogenesis in proliferating cells by regulating the trichoplein–Aurora A pathway

Inaba, Hironori; Goto, Hidemasa; Kasahara, Kousuke; Kumamoto, Kenzo; Yonemura, Shigenobu; Inoko, Akihito; Yamano, Shotaro; Wanibuchi, Hideki; He, Dongwei; Goshima, Naoki; Kiyono, Tohru; Hirotsune, Shinji; Inagaki, Masaki

doi:10.1083/jcb.201507046

Cited by 65 publications

(92 citation statements)

References 55 publications

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“…The process of ubiquitin-mediated protein degradation is required for cilium disassembly 58 , and trichoplein proteolysis is critical for the initiation of axoneme extension, indicating a similar requirement during cilium assembly 59,60 . Interestingly, a newly discovered protein, nuclear distribution element (NDE)-like 1 (Ndel1), functions in the trichoplein–Aurora-A pathway, and similarly to trichoplein depletion, loss of Ndel1 triggers aberrant ciliogenesis in growing cells 61 . Further, Ndel1 blocks ciliogenesis prior to axoneme extension by stabilizing trichoplein at mother centrioles, perhaps by protecting trichoplein from ubiquitin-mediated destruction.…”

Section: Cilium Disassemblymentioning

confidence: 99%

Cilium assembly and disassembly

2016

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The primary cilium is an antenna-like, immotile organelle present on most types of mammalian cells, which interprets extracellular signals that regulate growth and development. Although once considered a vestigial organelle, the primary cilium is now the focus of considerable interest. We now know that ciliary defects lead to a panoply of human diseases, termed ciliopathies, and the loss of this organelle may be an early signature event during oncogenic transformation. Ciliopathies include numerous seemingly unrelated developmental syndromes, with involvement of the retina, kidney, liver, pancreas, skeletal system and brain. Recent studies have begun to clarify the key mechanisms that link cilium assembly and disassembly to the cell cycle, and suggest new possibilities for therapeutic intervention.

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Section: Cilium Disassemblymentioning

confidence: 99%

Cilium assembly and disassembly

2016

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“…[30] In derived from the mother centriole and has distal and subdistal appendages and docks to the apical plasma membrane through the distal appendage. [25,26,[41][42][43] These findings suggest that primary cilia themselves can work as negative regulators of the cell cycle. The transition zone is a short (0.5 µm) area located above the basal body, characterized by Y-shaped connectors between the microtubule doublets and primary cilia membrane.…”

Section: Introductionmentioning

confidence: 98%

Primary Cilia as Signaling Hubs in Health and Disease

et al. 2018

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Primary cilia detect extracellular cues and transduce these signals into cells to regulate proliferation, migration, and differentiation. Here, the function of primary cilia as signaling hubs of growth factors and morphogens is in focus. First, the molecular mechanisms regulating the assembly and disassembly of primary cilia are described. Then, the role of primary cilia in mediating growth factor and morphogen signaling to maintain human health and the potential mechanisms by which defects in these pathways contribute to human diseases, such as ciliopathy, obesity, and cancer are described. Furthermore, a novel signaling pathway by which certain growth factors stimulate cell proliferation through suppression of ciliogenesis is also described, suggesting novel therapeutic targets in cancer.

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“…Co-IP was performed using Protein G Dynabeads according to the manufacturer's protocol (1003D, Thermo Fischer Scientific). Antibodies used for co-IP were KPL2end and DYNC1I2 (ProteinTech, 12219-1-AP) (Inaba et al, 2016). Antibody qualification data are presented in Fig.…”

Section: Co-immunoprecipitation (Co-ip) and Western Blotmentioning

confidence: 99%

SPEF2 functions in microtubule-mediated transport in elongating spermatids to ensure proper male germ cell differentiation

et al. 2017

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Sperm differentiation requires specific protein transport for correct sperm tail formation and head shaping. A transient microtubular structure, the manchette, appears around the differentiating spermatid head and serves as a platform for protein transport to the growing tail. Sperm flagellar 2 (SPEF2) is known to be essential for sperm tail development. In this study we investigated the function of SPEF2 during spermatogenesis using a male germ cell-specific Spef2 knockout mouse model. In addition to defects in sperm tail development, we observed a duplication of the basal body and failure in manchette migration resulting in an abnormal head shape. We identified cytoplasmic dynein 1 and GOLGA3 as novel interaction partners for SPEF2. SPEF2 and dynein 1 colocalize in the manchette and the inhibition of dynein 1 disrupts the localization of SPEF2 to the manchette. Furthermore, the transport of a known SPEF2-binding protein, IFT20, from the Golgi complex to the manchette was delayed in the absence of SPEF2. These data indicate a possible novel role of SPEF2 as a linker protein for dynein 1-mediated cargo transport along microtubules.

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Ndel1 suppresses ciliogenesis in proliferating cells by regulating the trichoplein–Aurora A pathway

Abstract: Ndel1, a protein located at the subdistal appendage of mother centriole, functions as an upstream regulator of the trichoplein–Aurora A pathway that suppresses ciliogenesis in proliferating cells.

Cited by 65 publications

References 55 publications

Cilium assembly and disassembly

Cilium assembly and disassembly

Primary Cilia as Signaling Hubs in Health and Disease

SPEF2 functions in microtubule-mediated transport in elongating spermatids to ensure proper male germ cell differentiation

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