Visualizing mechanosensory endings of TrkC‐expressing neurons in HS3ST‐2‐hPLAP mice

Hasegawa, Hiroshi; Wang, Fan

doi:10.1002/cne.21862

Cited by 27 publications

(29 citation statements)

References 58 publications

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“…39 Quantification of Hs3st expression by qPCR confirmed gene dosage-dependent loss of Hs3st2 expression in DRGs and no compensatory increase in expression of other Hs3sts (Figure 6a). Notably, growth cone collapse was diminished in a gene dosage dependent manner when stimulated by 10 ng/mL Sema3a ( P < 0.05; Figure 6g).…”

Section: Resultsmentioning

confidence: 61%

Expanding the 3-O-Sulfate Proteome—Enhanced Binding of Neuropilin-1 to 3-O-Sulfated Heparan Sulfate Modulates Its Activity

et al. 2016

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Binding of proteins to heparan sulfate is driven predominantly by electrostatic interactions between positively charged amino acid residues in the protein and negatively charged sulfate groups located at various positions along the polysaccharide chain. Although many heparin/heparan-sulfate-binding proteins have been described, few exhibit preferential binding for heparan sulfates containing relatively rare 3-O-sulfated glucosamine residues. To expand the “3-O-sulfate proteome,” affinity matrices were created from Chinese hamster ovary (CHO) cell heparan sulfate engineered in vitro with and without 3-O-sulfate groups. Fractionation of different animal sera yielded several proteins that bound specifically to columns containing 3-O-sulfated heparan sulfate modified by two members of the heparan sulfate 3-O-sulfotransferase superfamily, Hs3st1 and Hs3st2. Neuropilin-1 was analyzed in detail because it has been implicated in angiogenesis and axon guidance. We show that 3-O-sulfation enhanced the binding of neuropilin-1 to heparan sulfate immobilized on plastic plates and to heparan sulfate present on cultured cells. Chemoenzymatically synthesized 3-O-sulfated heparan sulfate dodecamers protected neuropilin-1 from thermal denaturation and inhibited neuropilin-1-dependent, semaphorin-3a-induced growth cone collapse of neurons derived from murine dorsal root ganglia. The effect of 3-O-sulfation was cell autonomous and specific to Hs3st2 based on collapse assays of neurons derived from Hs3st1- and Hs3st2-deficient mice. Finally, 3-O-sulfated heparan sulfate enhanced the inhibition of endothelial cell sprouting by exogenous heparan sulfate. These findings demonstrate a reliable method to identify members of the 3-O-sulfate proteome and that 3-O-sulfation of heparan sulfate can modulate axonal growth cone collapse and endothelial cell sprouting.

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Section: Resultsmentioning

confidence: 61%

Expanding the 3-O-Sulfate Proteome—Enhanced Binding of Neuropilin-1 to 3-O-Sulfated Heparan Sulfate Modulates Its Activity

et al. 2016

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“…Whole mount in situ hybridization demonstrated unique expression patterns of each of the Hs3st genes in the Zebrafish brain (Cadwallader and Yost, 2006). Studies of a transgenic mouse, in which the human placental alkaline phosphatase (hPLAP) was inserted next to the start codon of Hs3st-2 , showed expression in trigeminal and dorsal root ganglia during development (Hasegawa and Wang, 2008). Expression of Hs3st-2 and − 4 appeared associated with a subset of neuronal cells within the trigeminal ganglia (Lawrence et al, 2007).…”

Section: Expression Patterns Of the Hs3stsmentioning

confidence: 99%

Heparan sulfate 3-O-sulfation: A rare modification in search of a function

Thacker¹,

Xu²,

Lawrence³

et al. 2014

Matrix Biology

199

244

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Many protein ligands bind to heparan sulfate, which results in their presentation, protection, oligomerization or conformational activation. Binding depends on the pattern of sulfation and arrangement of uronic acid epimers along the chains. Sulfation at the C3 position of glucosamine is a relatively rare, yet biologically significant modification, initially described as a key determinant for binding and activation of antithrombin and later for infection by Type I Herpes Simplex virus. In mammals, a family of seven heparan sulfate 3-O-sulfotransferases installs sulfate groups at this position and constitutes the largest group of sulfotransferases involved in heparan sulfate formation. However, to date very few proteins or biological systems have been described that are influenced by 3-O-sulfation. This review describes our current understanding of the prevalence and structure of 3-O-sulfation sites, expression and substrate specificity of the 3-O-sulfotransferase family and the emerging roles of 3-O-sulfation in biology.

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“…Loss of Hs3st1 results in postnatal lethality with intrauterine growth retardation (HajMohammadi et al, 2003) and mice deficient in Hs3st2 are viable (Hasegawa and Wang, 2008). Hs3st’s have distinct roles in other organisms.…”

Section: Introductionmentioning

confidence: 99%

Hs3st3-Modified Heparan Sulfate Controls KIT+ Progenitor Expansion by Regulating 3-O-Sulfotransferases

et al. 2014

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Summary The exquisite control of growth factor function by heparan sulfate (HS) is dictated by the tremendous structural heterogeneity of sulfated modifications. It is not known how specific HS structures control growth factor-dependent progenitor expansion during organogenesis. We isolated KIT+ progenitors from fetal salivary glands during a stage of rapid progenitor expansion and profiled HS biosynthetic enzyme expression. Enzymes generating a specific type of 3-O-sulfated-HS (3-O-HS) are enriched, and FGF10/FGFR2b signaling directly regulates their expression. Bioengineered 3-O-HS binds FGFR2b and stabilizes FGF10/FGFR2b complexes in a receptor- and growth factor-specific manner. Rapid autocrine feedback increases 3-O-HS, KIT and progenitor expansion. Knockdown of multiple Hs3st isoforms limits fetal progenitor expansion, but is rescued with bioengineered 3-O-HS, which also increases adult progenitor expansion. Rapidly altering a specific 3-O-sulfated epitope provides a cellular mechanism to modulate the response to FGFR2b signaling and control progenitor expansion. 3-O-HS may expand KIT+ progenitors in vitro for regenerative therapy.

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Visualizing mechanosensory endings of TrkC‐expressing neurons in HS3ST‐2‐hPLAP mice

Cited by 27 publications

References 58 publications

Expanding the 3-O-Sulfate Proteome—Enhanced Binding of Neuropilin-1 to 3-O-Sulfated Heparan Sulfate Modulates Its Activity

Expanding the 3-O-Sulfate Proteome—Enhanced Binding of Neuropilin-1 to 3-O-Sulfated Heparan Sulfate Modulates Its Activity

Heparan sulfate 3-O-sulfation: A rare modification in search of a function

Hs3st3-Modified Heparan Sulfate Controls KIT+ Progenitor Expansion by Regulating 3-O-Sulfotransferases

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