Thehedgehog-related genequa-1 is required for molting inCaenorhabditis elegans

Hao, Limin; Mukherjee, Krishanu; Liégeois, Samuel; Baillie, David L.; Labouesse, Michel; Bürglin, Thomas R.

doi:10.1002/dvdy.20721

Cited by 45 publications

(64 citation statements)

References 48 publications

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“…VHA-5 and actin microfilaments are jointly reorganized during molting: The finding that VHA-5 is required for cuticle formation prompted us to examine whether its expression changes during larval molts, as observed for many genes encoding cuticular proteins or proteins involved in their processing ( Johnstone 2000;Hashmi et al 2004;Frand et al 2005;Hao et al 2006). We did not see any major change in VHA-5 abundance during larval stages (not shown); however, we could see that its distribution changed from randomly organized spots at intermolts to aligned spots forming parallel circumferential bands at molts (Figure 8 and data not shown).…”

Section: Resultsmentioning

confidence: 99%

Genes Required for Osmoregulation and Apical Secretion in Caenorhabditis elegans

Liégeois¹,

Benedetto

Michaux³

et al. 2007

Genetics

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Few studies have investigated whether or not there is an interdependence between osmoregulation and vesicular trafficking. We previously showed that in Caenorhabditis elegans che-14 mutations affect osmoregulation, cuticle secretion, and sensory organ development. We report the identification of seven lethal mutations displaying che-14-like phenotypes, which define four new genes, rdy-1-rdy-4 (rod-like larval lethality and dye-filling defective). rdy-1, rdy-2, and rdy-4 mutations affect excretory canal function and cuticle formation. Moreover, rdy-1 and rdy-2 mutations reduce the amount of matrix material normally secreted by sheath cells in the amphid channel. In contrast, rdy-3 mutants have short cystic excretory canals, suggesting that it acts in a different process. rdy-1 encodes the vacuolar H 1 -ATPase a-subunit VHA-5, whereas rdy-2 encodes a new tetraspan protein. We suggest that RDY-1/VHA-5 acts upstream of RDY-2 and CHE-14 in some tissues, since it is required for their delivery to the epidermal, but not the amphid sheath, apical plasma membrane. Hence, the RDY-1/VHA-5 trafficking function appears essential in some cells and its proton pump function essential in others. Finally, we show that RDY-1/VHA-5 distribution changes prior to molting in parallel with that of actin microfilaments and propose a model for molting whereby actin provides a spatial cue for secretion.

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Section: Resultsmentioning

confidence: 99%

Genes Required for Osmoregulation and Apical Secretion in Caenorhabditis elegans

Liégeois¹,

Benedetto

Michaux³

et al. 2007

Genetics

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“…S3 M and N). Furthermore, the expression of GFP reporters for both QUA-1, a cuticle protein required for molting (27), and for LON-3, a cuticle collagen, was normal (Fig. S3 O-R).…”

Section: Thioredoxin Reductase 1 and Glutathione Reductase Are Essentmentioning

confidence: 99%

Selenoprotein TRXR-1 and GSR-1 are essential for removal of old cuticle during molting in Caenorhabditis elegans

Stenvall

Fierro-González

Swoboda

et al. 2011

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

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Selenoproteins, in particular thioredoxin reductase, have been implicated in countering oxidative damage occurring during aging but the molecular functions of these proteins have not been extensively investigated in different animal models. Here we demonstrate that TRXR-1 thioredoxin reductase, the sole selenoprotein in Caenorhabditis elegans, does not protect against acute oxidative stress but functions instead together with GSR-1 glutathione reductase to promote the removal of old cuticle during molting. We show that the oxidation state of disulfide groups in the cuticle is tightly regulated during the molting cycle, and that when trxr-1 and gsr-1 function is reduced, disulfide groups in the cuticle remain oxidized. A selenocysteine-to-cysteine TRXR-1 mutant fails to rescue molting defects. Furthermore, worms lacking SELB-1, the C. elegans homolog of Escherichia coli SelB or mammalian EFsec, a translation elongation factor known to be specific for selenocysteine in E. coli, fail to incorporate selenocysteine, and display the same phenotype as those lacking trxr-1. Thus, TRXR-1 function in the reduction of old cuticle is strictly selenocysteine dependent in the nematode. Exogenously supplied reduced glutathione reduces disulfide groups in the cuticle and induces apolysis, the separation of old and new cuticle, strongly suggesting that molting involves the regulated reduction of cuticle components driven by TRXR-1 and GSR-1. Using dauer larvae, we demonstrate that aged worms have a decreased capacity to molt, and decreased expression of GSR-1. Together, our results establish a function for the selenoprotein TRXR-1 and GSR-1 in the removal of old cuticle from the surface of epidermal cells.

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“…Positive regulators of molting include matrix metalloproteases (Davis et al 2004;Hashmi et al 2004;Suzuki et al 2004;Altincicek et al 2010;Kim et al 2011;Stepek et al 2011), which are important for digestion of the old cuticle or processing of the new cuticle precursors, as well as selenoproteins, which promote collagen cross-linking (Stenvall et al 2011). Other functional classes of molecules critical for molting include sterol-binding nuclear hormone receptors (NHRs) (Kostrouchova et al 1998(Kostrouchova et al , 2001Gissendanner and Sluder 2000;Hayes et al 2006;Monsalve and Frand 2012), enzymes controlling sterol and fatty acid synthesis (Jia et al 2002;Kuervers et al 2003;Entchev and Kurzchalia 2005;Li and Paik 2011), and hedgehog-related proteins (Zugasti et al 2005;Hao et al 2006), which are often modified by sterols (Wendler et al 2006) and are dependent on NHRs for expression (Kouns et al 2011). Accordingly, dietary cholesterol promotes normal molting (Yochem et al 1999;Merris et al 2003;Entchev and Kurzchalia 2005;Roudier et al 2005), along with the LRP-1/megalin lipoprotein receptor, which is thought to support lipid uptake by the epidermis (Yochem et al 1999;May et al 2007).…”

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confidence: 99%

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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Thehedgehog-related genequa-1 is required for molting inCaenorhabditis elegans

Cited by 45 publications

References 48 publications

Genes Required for Osmoregulation and Apical Secretion in Caenorhabditis elegans

Genes Required for Osmoregulation and Apical Secretion in Caenorhabditis elegans

Selenoprotein TRXR-1 and GSR-1 are essential for removal of old cuticle during molting in Caenorhabditis elegans

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

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