Specificity of TGFbeta signaling is conferred by distinct type I receptors and their associated SMAD proteins in Caenorhabditis elegans

Development ◽  
1999 ◽  
Vol 126 (2) ◽  
pp. 251-260 ◽  
Author(s):  
S. Krishna ◽  
L.L. Maduzia ◽  
R.W. Padgett
Keyword(s):  
Body Size ◽  
Receptor Tyrosine Kinase ◽  
Distinct Type ◽  
General Mechanism ◽  
Type I ◽  
Biological Functions ◽  
Signaling Specificity ◽  
C Elegans ◽  
Reduced Body ◽  
Smad Proteins

In C. elegans, the TGFbeta-like type II receptor daf-4 is required for two distinct signaling pathways. In association with the type I receptor daf-1, it functions in the dauer pathway. In addition, it is also required for body size determination and male tail patterning, roles which do not require daf-1. In an effort to determine how two different signals are transmitted through daf-4, we looked for other potential signaling partners for DAF-4. We have cloned and characterized a novel type I receptor and show that it is encoded by sma-6. Mutations in sma-6 generate the reduced body size (Sma) and abnormal mail tail (Mab) phenotypes identical to those observed in daf-4 and sma-2, sma-3, sma-4 mutants (C. elegans Smads), indicating that they function in a common signaling pathway. However, mutations in sma-6, sma-2, sma-3, or sma-4 do not produce constitutive dauers, which demonstrates that the unique biological functions of daf-4 are mediated by distinct type I receptors functioning in parallel pathways. We propose that the C. elegans model for TGFbeta-like signaling, in which distinct type I receptors determine specificity, may be a general mechanism of achieving specificity in other organisms. These findings distinguish between the manner in which signaling specificity is achieved in TGFbeta-like pathways and receptor tyrosine-kinase (RTK) pathways.

The expression of TGFβ signal transducers in the hypodermis regulates body size inC. elegans

Development ◽  
2002 ◽  
Vol 129 (21) ◽  
pp. 4989-4998 ◽  
Author(s):  
Jianjun Wang ◽  
Rafal Tokarz ◽  
Cathy Savage-Dunn
Keyword(s):  
Nervous System ◽  
Body Size ◽  
Protein Accumulation ◽  
Type I ◽  
Loss Of Function ◽  
Signal Transducers ◽  
C Elegans ◽  
Genetic Mosaic ◽  
Mosaic Analysis ◽  
Necessary And Sufficient

In C. elegans, a TGFβ-related signaling pathway regulates body size. Loss of function of the signaling ligand (dbl-1),receptors (daf-4 and sma-6) or Smads (sma-2, sma-3and sma-4) results in viable, but smaller animals because of a reduction in postembryonic growth. We have investigated the tissue specificity of this pathway in body size regulation. We show that different tissues are reduced in size by different proportions, with hypodermal blast cell size most closely proportional to body size. We show that SMA-3 Smad is expressed in pharynx, intestine and hypodermis, as has been previously reported for the type I receptor SMA-6. Furthermore, we find that SMA-3::GFP is nuclear localized in all of these tissues, and that nuclear localization is enhanced by SMA-6 activity. Interestingly, SMA-3 protein accumulation was found to be negatively regulated by the level of Sma/Mab pathway activity. Using genetic mosaic analysis and directed expression of SMA-3, we find that SMA-3 activity in the hypodermis is necessary and sufficient for normal body size. Asdbl-1 is expressed primarily in the nervous system, these results suggest a model in which postembryonic growth of hypodermal cells is regulated by TGFβ-related signaling from the nervous system to the hypodermis.

A BMP homolog acts as a dose-dependent regulator of body size and male tail patterning in Caenorhabditis elegans

Development ◽  
1999 ◽  
Vol 126 (2) ◽  
pp. 241-250 ◽  
Author(s):  
Y. Suzuki ◽  
M.D. Yandell ◽  
P.J. Roy ◽  
S. Krishna ◽  
C. Savage-Dunn ◽  
...  
Keyword(s):  
Body Size ◽  
Caenorhabditis Elegans ◽  
Expression Pattern ◽  
Genetic Interactions ◽  
Loss Of Function ◽  
Male Tail ◽  
C Elegans ◽  
Reduced Body ◽  
Smad Signaling Pathway ◽  
Dose Dependent

We cloned the dbl-1 gene, a C. elegans homolog of Drosophila decapentaplegic and vertebrate BMP genes. Loss-of-function mutations in dbl-1 cause markedly reduced body size and defective male copulatory structures. Conversely, dbl-1 overexpression causes markedly increased body size and partly complementary male tail phenotypes, indicating that DBL-1 acts as a dose-dependent regulator of these processes. Evidence from genetic interactions indicates that these effects are mediated by a Smad signaling pathway, for which DBL-1 is a previously unidentified ligand. Our study of the dbl-1 expression pattern suggests a role for neuronal cells in global size regulation as well as male tail patterning.

scholarly journals Structural basis for ALK2/BMPR2 receptor complex signaling through kinase domain oligomerization

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Christopher Agnew ◽  
Pelin Ayaz ◽  
Risa Kashima ◽  
Hanna S. Loving ◽  
Prajakta Ghatpande ◽  
...  
Keyword(s):  
Md Simulations ◽  
Kinase Domain ◽  
Structural Basis ◽  
Type I ◽  
Type Ii ◽  
Exchange Mass Spectrometry ◽  
Receptor Complexes ◽  
Bmp Receptors ◽  
Morphogenetic Protein ◽  
Smad Proteins

AbstractUpon ligand binding, bone morphogenetic protein (BMP) receptors form active tetrameric complexes, comprised of two type I and two type II receptors, which then transmit signals to SMAD proteins. The link between receptor tetramerization and the mechanism of kinase activation, however, has not been elucidated. Here, using hydrogen deuterium exchange mass spectrometry (HDX-MS), small angle X-ray scattering (SAXS) and molecular dynamics (MD) simulations, combined with analysis of SMAD signaling, we show that the kinase domain of the type I receptor ALK2 and type II receptor BMPR2 form a heterodimeric complex via their C-terminal lobes. Formation of this dimer is essential for ligand-induced receptor signaling and is targeted by mutations in BMPR2 in patients with pulmonary arterial hypertension (PAH). We further show that the type I/type II kinase domain heterodimer serves as the scaffold for assembly of the active tetrameric receptor complexes to enable phosphorylation of the GS domain and activation of SMADs.

Relationship between circadian period and body size in the tau-mutant golden hamster

2014 ◽  
Vol 92 (1) ◽  
pp. 27-33
Author(s):  
Roberto Refinetti
Keyword(s):  
Body Size ◽  
Single Gene ◽  
Pleiotropic Effect ◽  
Circadian Period ◽  
Golden Syrian Hamster ◽  
Casein Kinase 1 ◽  
Reduced Body ◽  
Short Period ◽  
Casein Kinase 1 Epsilon ◽  
Tau Mutation

The tau mutation in the golden (Syrian) hamster is a single gene mutation that drastically affects the speed of the circadian clock, in such a way that homozygous mutants have an endogenous circadian period of 20 h (compared with 24 h for wild-type hamsters). While studying the circadian system of tau-mutant hamsters during the past 25 years, several authors have noted an apparent relationship between circadian period and body size in these animals. This study, based on 181 hamsters from 24 litters, confirmed previous observations that a shorter circadian period is associated with smaller body size, documented a sex difference in this association, and evaluated several mechanisms that might explain the phenomenon (such as different organ sizes, body composition, and metabolic rate). The obtained evidence suggests that the reduced body size of short-period hamsters is likely a pleiotropic effect of the tau allele (an allele of the casein kinase 1 epsilon gene) rather than a consequence of the shortened circadian period.

Ituglanis compactus, a new species of catfish (Siluriformes: Trichomycteridae) from the rio Jari drainage, lower Amazon, Brazil 

Zootaxa ◽  
2017 ◽  
Vol 4244 (2) ◽  
pp. 207 ◽  
Author(s):  
ÍTHALO DA SILVA CASTRO ◽  
WOLMAR BENJAMIN WOSIACKI
Keyword(s):  
New Species ◽  
Body Size ◽  
Head Length ◽  
New Taxon ◽  
Pectoral Fin ◽  
Reduced Body ◽  
Weberian Apparatus ◽  
Fin Rays ◽  
A New Species ◽  
Pectoral Fin Rays

A new species of Ituglanis is described from rio Iratapuru, near the rio Jari, Amapá, Brazil. The new species is distinguished from all congeners by the reduced number of post-Weberian apparatus vertebrae (36 or 37); the low number of paired ribs (2); the low number of interopercular odontodes (12–15); the number of branchiostegal rays (7 or 8); the presence of elongated fontanel in parieto-supraoccipital; the pectoral-fin rays (i,5); head length (18.9–25.0); and the presence of pores supraorbital s1, infraorbitals i1 and i3 of the laterosensory system. The new taxon has a reduced body size and fully ossified skeleton, but does not display a large number of paedomorphic traits compared to congeners. Comments about taxonomy and intrageneric comparisons are made, and paedomorphic in Ituglanis is discussed. Thoughts about conservation of the new species are presented. 

scholarly journals Smad Proteins and Hepatocyte Growth Factor Control Parallel Regulatory Pathways That Converge on β1-Integrin To Promote Normal Liver Development

2001 ◽  
Vol 21 (15) ◽  
pp. 5122-5131 ◽  
Author(s):  
Michael Weinstein ◽  
Satdarshan P. S. Monga ◽  
Ye Liu ◽  
Steven G. Brodie ◽  
Yi Tang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Type I ◽  
Β1 Integrin ◽  
Adhesive Properties ◽  
Regulatory Pathways ◽  
Smad Proteins ◽  
Hepatocyte Growth

ABSTRACT Smads serve as intracellular mediators of transforming growth factor β (TGF-β) signaling. After phosphorylation by activated type I TGF-β receptors, Smad proteins translocate to the nucleus, where they serve as transcription factors and increase or decrease expression of TGF-β target genes. Mice lacking one copy each ofSmad2 and Smad3 suffered midgestation lethality due to liver hypoplasia and anemia, suggesting essential dosage requirements of TGF-β signal components. This is likely due to abnormal adhesive properties of the mutant hepatocytes, which may result from a decrease in the level of the β1-integrin and abnormal processing and localization of E-cadherin. Culture of mutant livers in vitro revealed the existence of a parallel developmental pathway mediated by hepatocyte growth factor (HGF), which could rescue the mutant phenotype independent of Smad activation. These pathways merge at the β1-integrin, the level of which was increased by HGF in the cultured mutant livers. HGF treatment reversed the defects in cell proliferation and hepatic architecture in theSmad2 +/− ; Smad3 +/− livers.

Methylation of the nuclear poly(A)-binding protein by type I protein arginine methyltransferases – how and why

2013 ◽  
Vol 394 (8) ◽  
pp. 1029-1043 ◽  
Author(s):  
Elmar Wahle ◽  
Bodo Moritz
Keyword(s):  
Active Sites ◽  
Binding Protein ◽  
Arginine Methylation ◽  
Fine Tuning ◽  
General Mechanism ◽  
Type I ◽  
Protein Arginine Methyltransferases ◽  
Low Protein ◽  
Backbone Conformation ◽  
Arginine Residues

Abstract Asymmetric dimethylation of arginine side chains in proteins is a frequent posttranslational modification, catalyzed by type I protein arginine methyltransferases (PRMTs). This article summarizes what is known about this modification in the nuclear poly(A)-binding protein (PABPN1). PABPN1 contains 13 dimethylated arginine residues in its C-terminal domain. Three enzymes, PRMT1, 3, and 6, can methylate PABPN1. Although 26 methyl groups are transferred to one PABPN1 molecule, the PRMTs do so in a distributive reaction, i.e., only a single methyl group is transferred per binding event. As PRMTs form dimers, with the active sites accessible from a small central cavity, backbone conformation around the methyl-accepting arginine is an important determinant of substrate specificity. Neither the association of PABPN1 with poly(A) nor its role in poly(A) tail synthesis is affected by arginine methylation. At least at low protein concentration, methylation does not affect the protein’s tendency to oligomerize. The dimethylarginine residues of PABPN1 are located in the binding site for its nuclear import receptor, transportin. Arginine methylation weakens this interaction about 10-fold. Very recent evidence suggests that arginine methylation as a way of fine-tuning the interactions between transportin and its cargo may be a general mechanism.

scholarly journals Convergence in reduced body size, head size, and blood glucose in three island reptiles

2018 ◽  
Vol 8 (12) ◽  
pp. 6169-6182 ◽  
Author(s):  
Amanda M. Sparkman ◽  
Amanda D. Clark ◽  
Lilly J. Brummett ◽  
Kenneth R. Chism ◽  
Lucia L. Combrink ◽  
...  
Keyword(s):  
Body Size ◽  
Blood Glucose ◽  
Head Size ◽  
Reduced Body
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