Nek9, Nek6, Nek7 and the separation of centrosomes

Sdelci, Sara; Bertran, M. Teresa; Roig, Joan

doi:10.4161/cc.10.22.18226

Cited by 32 publications

(24 citation statements)

References 6 publications

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“…In the case of the mammalian NEKL-3 orthologs, NEK6 and NEK7, the majority of studies have focused on the role of these kinases in the cell division process including centrosome separation (Sdelci et al 2011), spindle formation, and cytokinesis (O'Regan et al 2007;O'Regan and Fry 2009). These functions also link well to the reported involvement of NEK6 and NEK7 in tumorigenesis (Nassirpour et al 2010;Wang et al 2013;Zhou et al 2016).…”

Section: Discussionmentioning

confidence: 89%

Conserved Ankyrin Repeat Proteins and Their NIMA Kinase Partners Regulate Extracellular Matrix Remodeling and Intracellular Trafficking inCaenorhabditis elegans

Lažetić¹,

Fay

2017

Genetics

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Molting is an essential developmental process in nematodes during which the epidermal apical extracellular matrix, the cuticle, is remodeled to accommodate further growth. Using genetic approaches, we identified a requirement for three conserved ankyrin repeat-rich proteins, MLT-2/ANKS6, MLT-3/ANKS3, and MLT-4/INVS, in Caenorhabditis elegans molting. Loss of mlt function resulted in severe defects in the ability of larvae to shed old cuticle and led to developmental arrest. Genetic analyses demonstrated that MLT proteins functionally cooperate with the conserved NIMA kinase family members NEKL-2/NEK8 and NEKL-3/NEK6/NEK7 to promote cuticle shedding. MLT and NEKL proteins were specifically required within the hyp7 epidermal syncytium, and fluorescently tagged mlt and nekl alleles were expressed in puncta within this tissue. Expression studies further showed that NEKL-2-MLT-2-MLT-4 and NEKL-3-MLT-3 colocalize within largely distinct assemblies of apical foci. MLT-2 and MLT-4 were required for the normal accumulation of NEKL-2 at the hyp7-seam cell boundary, and loss of mlt-2 caused abnormal nuclear accumulation of NEKL-2. Correspondingly, MLT-3, which bound directly to NEKL-3, prevented NEKL-3 nuclear localization, supporting the model that MLT proteins may serve as molecular scaffolds for NEKL kinases. Our studies additionally showed that the NEKL-MLT network regulates early steps in clathrin-mediated endocytosis at the apical surface of hyp7, which may in part account for molting defects observed in nekl and mlt mutants. This study has thus identified a conserved NEKL-MLT protein network that regulates remodeling of the apical extracellular matrix and intracellular trafficking, functions that may be conserved across species.KEYWORDS C. elegans; molting; NIMA kinase; endocytosis; ankyrin repeat proteins M OLTING is a ubiquitous process in nematode species, including Caenorhabditis elegans, and is required for organismal growth and development. Although the observable biomechanics and major morphological features of C. elegans molting were first described nearly 40 years ago (Hirsh et al. 1976;Singh and Sulston 1978), the molecular and cellular mechanisms underlying this complex process are largely unknown. Notably, molting occurs in both pathogenic and nonpathogenic nematode species, and molting factors have been proposed as potential targets for antiparasitic drugs (Page et al. 2014;Gooyit et al. 2015).Mechanistically, molting is the process by which nematodes remodel their epidermal apical extracellular matrix (ECM), termed the cuticle. In C. elegans larvae and adults, the cuticle serves as a mechanical barrier and provides physical and chemical protection from the environment (Page and Johnstone 2007). In addition, similar to the chitin-based exoskeleton of insects and other arthropods, the cuticle is required to facilitate organismal movement in conjunction with attached underlying muscles. Unlike arthropods, however, in nematodes the cuticle is comprised primarily of collagens (Page and Johnstone 20...

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Section: Discussionmentioning

confidence: 89%

Conserved Ankyrin Repeat Proteins and Their NIMA Kinase Partners Regulate Extracellular Matrix Remodeling and Intracellular Trafficking inCaenorhabditis elegans

Lažetić¹,

Fay

2017

Genetics

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“…Activated Nek6/ Nek7 in turn phosphorylate the kinesin Eg5, which leads to its accumulation at the centrosomes and controls centrosome separation and normal mitotic spindle formation [9]. Besides the shared role in spindle formation, characterization of the Nek7 proteome suggests that Nek7 acts in different cellular processes independently of Nek6 [10].…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

Anks3 alters the sub-cellular localization of the Nek7 kinase

Ramachandran

Engel

Müller

et al. 2015

Biochemical and Biophysical Research Communications

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“…However, it is likely that there are other components of this linker structure that might also be regulated by NEK2, including both CEP68 and b-catenin (Bahmanyar et al, 2008;Graser et al, 2007). Whereas disjunction of centrosomes by NEK2 facilitates spindle pole separation at the onset of mitosis, NEK6, NEK7 and NEK9 have other important roles in generating the mitotic spindle (O'Regan et al, 2007;Sdelci et al, 2011). These three proteins act in concert, whereby NEK9 is an upstream activator of NEK6 and NEK7 (Belham et al, 2003).…”

Section: The Role Of Neks In Mitotic Entrymentioning

confidence: 99%

Cell cycle regulation by the NEK family of protein kinases

Fry

O’Regan

Sabir

et al. 2012

Journal of Cell Science

308

322

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SummaryGenetic screens for cell division cycle mutants in the filamentous fungus Aspergillus nidulans led to the discovery of never-in-mitosis A (NIMA), a serine/threonine kinase that is required for mitotic entry. Since that discovery, NIMA-related kinases, or NEKs, have been identified in most eukaryotes, including humans where eleven genetically distinct proteins named NEK1 to NEK11 are expressed. Although there is no evidence that human NEKs are essential for mitotic entry, it is clear that several NEK family members have important roles in cell cycle control. In particular, NEK2, NEK6, NEK7 and NEK9 contribute to the establishment of the microtubulebased mitotic spindle, whereas NEK1, NEK10 and NEK11 have been implicated in the DNA damage response. Roles for NEKs in other aspects of mitotic progression, such as chromatin condensation, nuclear envelope breakdown, spindle assembly checkpoint signalling and cytokinesis have also been proposed. Interestingly, NEK1 and NEK8 also function within cilia, the microtubule-based structures that are nucleated from basal bodies. This has led to the current hypothesis that NEKs have evolved to coordinate microtubule-dependent processes in both dividing and non-dividing cells. Here, we review the functions of the human NEKs, with particular emphasis on those family members that are involved in cell cycle control, and consider their potential as therapeutic targets in cancer.

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Nek9, Nek6, Nek7 and the separation of centrosomes

Cited by 32 publications

References 6 publications

Conserved Ankyrin Repeat Proteins and Their NIMA Kinase Partners Regulate Extracellular Matrix Remodeling and Intracellular Trafficking inCaenorhabditis elegans

Conserved Ankyrin Repeat Proteins and Their NIMA Kinase Partners Regulate Extracellular Matrix Remodeling and Intracellular Trafficking inCaenorhabditis elegans

Anks3 alters the sub-cellular localization of the Nek7 kinase

Cell cycle regulation by the NEK family of protein kinases

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