The Cooperation of FGF Receptor and Klotho Is Involved in Excretory Canal Development and Regulation of Metabolic Homeostasis in Caenorhabditis elegans

Polanska, Urszula M.; Edwards, Elisabeth; Fernig, David G.; Kinnunen, Tarja

doi:10.1074/jbc.m110.173039

Cited by 25 publications

(29 citation statements)

References 42 publications

(23 reference statements)

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“…More details on the mouse Klotho gene and the identification of the human (96% homology) as well as the rat Klotho gene were reported 1 year later ; two distinct transcripts encoding membrane and secreted Klotho protein were characterized. Klotho has been identified not only in the zebrafish, Danio rerio, but two Klotho-like genes, klo1 and klo2, have also been identified in the nematode Caenorhabditis elegans (Polanska et al 2011, Sugano & Lardelli 2011, Mangos et al 2012. The corresponding KLO1 and KLO2 proteins lack a transmembrane domain.…”

Section: Klotho a Transmembrane Co-receptor And A Multifunctional Humentioning

confidence: 99%

“…The ancestral 'truncated' Klotho forms in nematodes contain only one KL domain and lack the second internal repeat (whereas the full-length transmembrane vertebral Klothos are composed of two KL domains). Therefore, they correspond more closely to the alternatively spliced form for the shorter, directly secreted isoform in men (Polanska et al 2011).…”

Section: Klotho a Transmembrane Co-receptor And A Multifunctional Humentioning

confidence: 99%

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Growth hormone and Klotho

Schmid

Neidert

Tschopp

et al. 2013

Journal of Endocrinology

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Acromegaly is characterized by excessively high GH and IGF1 levels. Recent data suggest that soluble Klotho (sKlotho) is also elevated in patients with active acromegaly. sKlotho decreases towards normal following removal of the GH-producing pituitary adenoma. The Klotho gene was identified in mice following its accidental disruption by ectopic DNA. It is an ageing suppressor gene of restricted expression (mainly in kidneys, brain, and parathyroid and pituitary glands) encoding a transmembrane protein, mKlotho. mKlotho serves as a co-receptor in fibroblast growth factor 23 (FGF23) signalling. FGF23 promotes urinary phosphate excretion and inhibits the synthesis of calcitriol. The ectodomain of mKlotho is enzymatically released to result in a humoral factor, sKlotho, which exerts systemic effects (on ion channels and signalling pathways), possibly by working as an enzyme that modifies glycans of cell surface glycoproteins. GH enhances renal phosphate reabsorption and calcitriol production, i.e. exerts effects in the proximal tubule opposing those attributed to mKlotho, and attenuates calciuria in the distal tubule similar to sKlotho. sKlotho can be measured in extracellular fluids (serum, urine and cerebrospinal fluid (CSF)) by an ELISA. In line with predominant expression of Klotho in kidneys and choroid plexus, concentrations of sKlotho are particularly high in urine and CSF. Determination of sKlotho in serum and urine (both presumably reflecting GH action on the kidneys) could be used as a supplementary tool in the diagnosis and follow-up of patients with acromegaly. The question arises whether GH exerts selected actions via modifying activities of Klotho.

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Section: Klotho a Transmembrane Co-receptor And A Multifunctional Humentioning

confidence: 99%

Section: Klotho a Transmembrane Co-receptor And A Multifunctional Humentioning

confidence: 99%

Growth hormone and Klotho

Schmid

Neidert

Tschopp

et al. 2013

Journal of Endocrinology

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“…EGL-15 is N-glycosylated in vivo and this modification appears to negatively regulate its activity, potentially by interfering with ligand binding or self-association (Polanska et al, 2009). EGL-15A activity may be positively regulated by two C. elegans orthlogs of Klotho, a mammalian FGFR binding protein and co-receptor (Chateau et al, 2010; Polanska et al, 2011). …”

Section: Regulators and Targets Of Rtk Activitymentioning

confidence: 99%

Canonical RTK-Ras-ERK signaling and related alternative pathways

Sundaram¹

2013

WormBook

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Receptor Tyrosine Kinase (RTK)-Ras-Extracellular signal-regulated kinase (ERK) signaling pathways control many aspects of C. elegans development and behavior. Studies in C. elegans helped elucidate the basic framework of the RTK-Ras-ERK pathway and continue to provide insights into its complex regulation, its biological roles, how it elicits cell-type appropriate responses, and how it interacts with other signaling pathways to do so. C. elegans studies have also revealed biological contexts in which alternative RTK- or Ras-dependent pathways are used instead of the canonical pathway.

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“…To adopt its distinctive H-shape, the canal cell undergoes an extensive program of elongation and branching that is regulated by neural guidance cues such as netrins, Wnts, and FGFs and by other factors in the extracellular matrix such as collagens and laminins (Hedgecock et al 1987;Buechner 2002;Oosterveen et al 2007;Polanska et al 2011). Once born, the canal cell begins to grow out left and right over the ventral muscle quadrants from the cell body to the lateral surface.…”

Section: Transcription Factors Important For Canal Cell Differentiationmentioning

confidence: 99%

“…Supporting the second possibility, the canal synthesizes several matrix metalloproteases (Spencer et al 2011) that could be used for cutting through the basement membrane. In addition to the guidance cues mentioned above, multiple other genes and pathways that affect the extent of canal outgrowth appear to function in the hypodermis or in other nearby tissues over which the canal grows (Polanska et al 2011;MarcusGueret et al 2012).…”

Section: Transcription Factors Important For Canal Cell Differentiationmentioning

confidence: 99%

The Caenorhabditis elegans Excretory System: A Model for Tubulogenesis, Cell Fate Specification, and Plasticity

Sundaram

Buechner

2016

Genetics

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The excretory system of the nematode Caenorhabditis elegans is a superb model of tubular organogenesis involving a minimum of cells. The system consists of just three unicellular tubes (canal, duct, and pore), a secretory gland, and two associated neurons. Just as in more complex organs, cells of the excretory system must first adopt specific identities and then coordinate diverse processes to form tubes of appropriate topology, shape, connectivity, and physiological function. The unicellular topology of excretory tubes, their varied and sometimes complex shapes, and the dynamic reprogramming of cell identity and remodeling of tube connectivity that occur during larval development are particularly fascinating features of this organ. The physiological roles of the excretory system in osmoregulation and other aspects of the animal's life cycle are only beginning to be explored. The cellular mechanisms and molecular pathways used to build and shape excretory tubes appear similar to those used in both unicellular and multicellular tubes in more complex organs, such as the vertebrate vascular system and kidney, making this simple organ system a useful model for understanding disease processes.KEYWORDS Caenorhabditis elegans; tubulogenesis; excretory-secretory system; WormBook

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The Cooperation of FGF Receptor and Klotho Is Involved in Excretory Canal Development and Regulation of Metabolic Homeostasis in Caenorhabditis elegans

Cited by 25 publications

References 42 publications

Growth hormone and Klotho

Growth hormone and Klotho

Canonical RTK-Ras-ERK signaling and related alternative pathways

The Caenorhabditis elegans Excretory System: A Model for Tubulogenesis, Cell Fate Specification, and Plasticity

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