scholarly journals Perlecan regulates bidirectional Wnt signaling at the Drosophila neuromuscular junction

2013 ◽  
Vol 200 (2) ◽  
pp. 219-233 ◽  
Author(s):  
Keisuke Kamimura ◽  
Kohei Ueno ◽  
Jun Nakagawa ◽  
Rie Hamada ◽  
Minoru Saitoe ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Neuromuscular Junction ◽  
Heparan Sulfate ◽  
Wnt Signaling ◽  
Nuclear Import ◽  
Heparan Sulfate Proteoglycans ◽  
Down Regulation ◽  
Bidirectional Signaling ◽  
Synaptic Boutons ◽  
Signaling Activity

Heparan sulfate proteoglycans (HSPGs) play pivotal roles in the regulation of Wnt signaling activity in several tissues. At the Drosophila melanogaster neuromuscular junction (NMJ), Wnt/Wingless (Wg) regulates the formation of both pre- and postsynaptic structures; however, the mechanism balancing such bidirectional signaling remains elusive. In this paper, we demonstrate that mutations in the gene of a secreted HSPG, perlecan/trol, resulted in diverse postsynaptic defects and overproduction of synaptic boutons at NMJ. The postsynaptic defects, such as reduction in subsynaptic reticulum (SSR), were rescued by the postsynaptic activation of the Frizzled nuclear import Wg pathway. In contrast, overproduction of synaptic boutons was suppressed by the presynaptic down-regulation of the canonical Wg pathway. We also show that Trol was localized in the SSR and promoted postsynaptic accumulation of extracellular Wg proteins. These results suggest that Trol bidirectionally regulates both pre- and postsynaptic activities of Wg by precisely distributing Wg at the NMJ.

scholarly journals Heparan sulfate proteoglycans are critical for the organization of the extracellular distribution of Wingless

Development ◽  
2001 ◽  
Vol 128 (1) ◽  
pp. 87-94 ◽  
Author(s):  
G.H. Baeg ◽  
X. Lin ◽  
N. Khare ◽  
S. Baumgartner ◽  
N. Perrimon
Keyword(s):  
Heparan Sulfate ◽  
Wnt Signaling ◽  
Heparan Sulfate Proteoglycans ◽  
Gene Activity ◽  
Dramatic Decrease

Recent studies in Drosophila have shown that heparan sulfate proteoglycans (HSPGs) are required for Wingless (Wg/Wnt) signaling. In addition, genetic and phenotypic analyses have implicated the glypican gene dally in this process. Here, we report the identification of another Drosophila glypican gene, dally-like (dly) and show that it is also involved in Wg signaling. Inhibition of dly gene activity implicates a function for DLY in Wg reception and we show that overexpression of DLY leads to an accumulation of extracellular Wg. We propose that DLY plays a role in the extracellular distribution of Wg. Consistent with this model, a dramatic decrease of extracellular Wg was detected in clones of cells that are deficient in proper glycosaminoglycan biosynthesis. We conclude that HSPGs play an important role in organizing the extracellular distribution of Wg.

scholarly journals Coordination of Heparan Sulfate Proteoglycans with Wnt Signaling To Control Cellular Migrations and Positioning in Caenorhabditis elegans

Genetics ◽  
2017 ◽  
Vol 206 (4) ◽  
pp. 1951-1967 ◽  
Author(s):  
Kristian Saied-Santiago ◽  
Robert A. Townley ◽  
John D. Attonito ◽  
Dayse S. da Cunha ◽  
Carlos A. Díaz-Balzac ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Heparan Sulfate ◽  
Wnt Signaling ◽  
Heparan Sulfate Proteoglycans

scholarly journals QSulf1 remodels the 6-O sulfation states of cell surface heparan sulfate proteoglycans to promote Wnt signaling

2003 ◽  
Vol 162 (2) ◽  
pp. 341-351 ◽  
Author(s):  
Xingbin Ai ◽  
Anh-Tri Do ◽  
Olga Lozynska ◽  
Marion Kusche-Gullberg ◽  
Ulf Lindahl ◽  
...  
Keyword(s):  
Cell Surface ◽  
Heparan Sulfate ◽  
Wnt Signaling ◽  
Present Model ◽  
Receptor Activation ◽  
Heparan Sulfate Proteoglycans ◽  
Biochemical Studies ◽  
Frizzled Receptors ◽  
Wnt Signal ◽  
Function Cell

The 6-O sulfation states of cell surface heparan sulfate proteoglycans (HSPGs) are dynamically regulated to control the growth and specification of embryonic progenitor lineages. However, mechanisms for regulation of HSPG sulfation have been unknown. Here, we report on the biochemical and Wnt signaling activities of QSulf1, a novel cell surface sulfatase. Biochemical studies establish that QSulf1 is a heparan sulfate (HS) 6-O endosulfatase with preference, in particular, toward trisulfated IdoA2S-GlcNS6S disaccharide units within HS chains. In cells, QSulf1 can function cell autonomously to remodel the sulfation of cell surface HS and promote Wnt signaling when localized either on the cell surface or in the Golgi apparatus. QSulf1 6-O desulfation reduces XWnt binding to heparin and HS chains of Glypican1, whereas heparin binds with high affinity to XWnt8 and inhibits Wnt signaling. CHO cells mutant for HS biosynthesis are defective in Wnt-dependent Frizzled receptor activation, establishing that HS is required for Frizzled receptor function. Together, these findings suggest a two-state “catch or present” model for QSulf1 regulation of Wnt signaling in which QSulf1 removes 6-O sulfates from HS chains to promote the formation of low affinity HS–Wnt complexes that can functionally interact with Frizzled receptors to initiate Wnt signal transduction.

scholarly journals Host Glycosaminoglycan Confers Susceptibility to Bacterial Infection in Drosophila melanogaster

2008 ◽  
Vol 77 (2) ◽  
pp. 860-866 ◽  
Author(s):  
Miriam J. Baron ◽  
Sandra L. Wong ◽  
Kent Nybakken ◽  
Vincent J. Carey ◽  
Lawrence C. Madoff
Keyword(s):  
Drosophila Melanogaster ◽  
Heparan Sulfate ◽  
Group B Streptococcus ◽  
Heparan Sulfate Proteoglycans ◽  
Bacterial Killing ◽  
C Protein ◽  
Susceptibility To Infection ◽  
Anchoring Proteins ◽  
Group B ◽  
Streptococcus A

ABSTRACT Many pathogens engage host cell surface glycosaminoglycans, but redundancy in pathogen adhesins and host glycosaminoglycan-anchoring proteins (heparan sulfate proteoglycans) has limited the understanding of the importance of glycosaminoglycan binding during infection. The alpha C protein of group B streptococcus, a virulence determinant for this neonatal human pathogen, binds to host glycosaminoglycan and mediates the entry of bacteria into human cells. We studied alpha C protein-glycosaminoglycan binding in Drosophila melanogaster, whose glycosaminoglycan repertoire resembles that of humans but whose genome includes only three characterized membrane heparan sulfate proteoglycan genes. The knockdown of glycosaminoglycan polymerases or of heparan sulfate proteoglycans reduced the cellular binding of alpha C protein. The interruption of alpha C protein-glycosaminoglycan binding was associated with longer host survival and a lower bacterial burden. These data indicate that the glycosaminoglycan-alpha C protein interaction involves multiple heparan sulfate proteoglycans and impairs bacterial killing. Host glycosaminoglycans, anchored by multiple proteoglycans, thereby determine susceptibility to infection. Because there is homology between Drosophila and human glycosaminoglycan/proteoglycan structures and many pathogens express glycosaminoglycan-binding structures, our data suggest that interfering with glycosaminoglycan binding may protect against infections in humans.

scholarly journals Author response: R-spondins engage heparan sulfate proteoglycans to potentiate WNT signaling

2020 ◽  
Author(s):  
Ramin Dubey ◽  
Peter van Kerkhof ◽  
Ingrid Jordens ◽  
Tomas Malinauskas ◽  
Ganesh V Pusapati ◽  
...  
Keyword(s):  
Heparan Sulfate ◽  
Wnt Signaling ◽  
Heparan Sulfate Proteoglycans ◽  
Author Response
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