NDP Kinase 7 Is a Conserved Microtubule-Binding Protein Preferentially Expressed in Ciliated Cells

Ikeda, Takashi

doi:10.1247/csf.09016

Cited by 19 publications

(15 citation statements)

References 37 publications

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“…This fruitful approach has shed light on evolutionary conserved mechanisms involved in Alzheimer's disease [15], ciliary function [24], or epithelial integrity [25]. Nevertheless, the need for studies of Nme functions in non-vertebrate model species was recently stressed by the scientific community [16].…”

Section: Resultsmentioning

confidence: 99%

“…They have been shown to play critical roles in spermatogenesis [33]–[35], sperm motility [2], development [36], and human conditions associated with primary ciliary dyskinesia [37]. The existence of orthologs in non-metazoan species was however unsuspected with the exception of the report of Nme7 in C. reinhardtii and T. thermophila [24]. In the present study, we have demonstrated that Nme5 , Nme6 , Nme7 , and Nme8 genes were present in the metazoan ancestor, while Nme5 , Nme6 , and Nme7 were most likely present in the eukaryote ancestor.…”

Section: Resultsmentioning

confidence: 99%

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Nme Gene Family Evolutionary History Reveals Pre-Metazoan Origins and High Conservation between Humans and the Sea Anemone, Nematostella vectensis

2010

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BackgroundThe Nme gene family is involved in multiple physiological and pathological processes such as cellular differentiation, development, metastatic dissemination, and cilia functions. Despite the known importance of Nme genes and their use as clinical markers of tumor aggressiveness, the associated cellular mechanisms remain poorly understood. Over the last 20 years, several non-vertebrate model species have been used to investigate Nme functions. However, the evolutionary history of the family remains poorly understood outside the vertebrate lineage. The aim of the study was thus to elucidate the evolutionary history of the Nme gene family in Metazoans.Methodology/Principal FindingsUsing a total of 21 eukaryote species including 14 metazoans, the evolutionary history of Nme genes was reconstructed in the metazoan lineage. We demonstrated that the complexity of the Nme gene family, initially thought to be restricted to chordates, was also shared by the metazoan ancestor. We also provide evidence suggesting that the complexity of the family is mainly a eukaryotic innovation, with the exception of Nme8 that is likely to be a choanoflagellate/metazoan innovation. Highly conserved gene structure, genomic linkage, and protein domains were identified among metazoans, some features being also conserved in eukaryotes. When considering the entire Nme family, the starlet sea anemone is the studied metazoan species exhibiting the most conserved gene and protein sequence features with humans. In addition, we were able to show that most of the proteins known to interact with human NME proteins were also found in starlet sea anemone.Conclusion/SignificanceTogether, our observations further support the association of Nme genes with key cellular functions that have been conserved throughout metazoan evolution. Future investigations of evolutionarily conserved Nme gene functions using the starlet sea anemone could shed new light on a wide variety of key developmental and cellular processes.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Nme Gene Family Evolutionary History Reveals Pre-Metazoan Origins and High Conservation between Humans and the Sea Anemone, Nematostella vectensis

2010

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“…Candidate cTuRC subunit; NDP kinase with function in motile cilia, the role in cTuRC is unknown (Choi et al, 2010;Hutchins et al, 2010;Ikeda, 2010;Teixido-Travesa et al, 2010;Vogel et al, 2010) LGALS3BP…”

Section: Nme7mentioning

confidence: 99%

The where, when and how of microtubule nucleation – one ring to rule them all

Teixidó-Travesa¹,

Roig

Lüders³

2012

Journal of Cell Science

153

162

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SummaryThe function of microtubules depends on their arrangement into highly ordered arrays. Spatio-temporal control over the formation of new microtubules and regulation of their properties are central to the organization of these arrays. The nucleation of new microtubules requires c-tubulin, an essential protein that assembles into multi-subunit complexes and is found in all eukaryotic organisms. However, the way in which c-tubulin complexes are regulated and how this affects nucleation and, potentially, microtubule behavior, is poorly understood. c-tubulin has been found in complexes of various sizes but several lines of evidence suggest that only large, ring-shaped complexes function as efficient microtubule nucleators. Human c-tubulin ring complexes (cTuRCs) are composed of c-tubulin and the c-tubulin complex components (GCPs) 2, 3, 4, 5 and 6, which are members of a conserved protein family. Recent work has identified additional unrelated cTuRC subunits, as well as a large number of more transient cTuRC interactors. In this Commentary, we discuss the regulation of cTuRC-dependent microtubule nucleation as a key mechanism of microtubule organization. Specifically, we focus on the regulatory roles of the cTuRC subunits and interactors and present an overview of other mechanisms that regulate cTuRC-dependent microtubule nucleation and organization.

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“…These proteins are associated with microtubules in vivo (in the case of NME5) or able to bind to microtubules in vitro (in the cases of NME7, NME8, and NME9) (Munier et al 2003;Sadek et al 2003;Duriez et al 2007;Ikeda 2010). Deficient ciliar/flagellar motility is associated with Kartagener syndrome, characterized by situs inversus, bronchiectasis, and sinusitis (Kartagener and Horlacher 1936) as well as other symptoms more generally defined as primary ciliary dyskinesia (Marshall 2008).…”

Section: Knockout Mouse Modelsmentioning

confidence: 99%

Learning about the functions of NME/NM23: lessons from knockout mice to silencing strategies

Boissan

Lacombe

2011

Naunyn-Schmiedeberg's Arch Pharmacol

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The human NME gene family (also known as NM23) comprises ten genes that are involved in diverse physiological and pathological processes including proliferation, differentiation, development, ciliary functions, and metastasis. For the moment, only the NME1, NME2, and NME7 genes have been inactivated in transgenic knockout mice, as well as a double NME1-NME2 gene knockout. Mice lacking NME1 or NME2 grow to adulthood without health problems, although NME1 (-/-) mice have modest growth retardation. Double knockout NME1 (-/-)-NME2 (-/-) mice, by contrast, are highly hypotrophic and die at birth from profound anemia due to impaired erythroblast development. Evidence for a metastasis suppressor function of NME1 in vivo comes from crossing NME1 (-/-) mice with mice prone to develop hepatocellular carcinoma; the double transgenic mice present a higher incidence of lung metastases. Silencing of NME1 by siRNA interference has confirmed this function by conferring a "metastatic phenotype" on non-invasive human epithelial cancer cell lines. This function is specific to NME1 and is not observed when the NME2 is silenced. The data indicate that NME1 loss is causally involved at the early stages of the metastatic cascade. NME2 (-/-) mice and NME2 silencing experiments reveal a specific role of NME2 in activation of heterotrimeric G proteins and of KCa3.1 channel in T cells, pointing to a role of NME2 as a histidine phosphotransferase. Regarding NME7, consistent with its expression in axonemal structures, NME7 (-/-) mice present lesions similar to primary ciliary dyskinesia. This review summarizes the recent data obtained by knockout and silencing of NME/NM23 genes that provide mechanistic insights into their respective roles in physiology and pathology.

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NDP Kinase 7 Is a Conserved Microtubule-Binding Protein Preferentially Expressed in Ciliated Cells

Cited by 19 publications

References 37 publications

Nme Gene Family Evolutionary History Reveals Pre-Metazoan Origins and High Conservation between Humans and the Sea Anemone, Nematostella vectensis

Nme Gene Family Evolutionary History Reveals Pre-Metazoan Origins and High Conservation between Humans and the Sea Anemone, Nematostella vectensis

The where, when and how of microtubule nucleation – one ring to rule them all

Learning about the functions of NME/NM23: lessons from knockout mice to silencing strategies

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