Specific and Flexible Roles of Heparan Sulfate Modifications in Drosophila FGF Signaling

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2006 Sep 13

PMID 16966419

Citations 67

Authors

Keisuke Kamimura

Takashi Koyama

Hiroko Habuchi

Ryu Ueda

Masayuki Masu

Koji Kimata

Hiroshi Nakato

Affiliations

Soon will be listed here.

Abstract

Specific sulfation sequence of heparan sulfate (HS) contributes to the selective interaction between HS and various proteins in vitro. To clarify the in vivo importance of HS fine structures, we characterized the functions of the Drosophila HS 2-O and 6-O sulfotransferase (Hs2st and Hs6st) genes in FGF-mediated tracheal formation. We found that mutations in Hs2st or Hs6st had unexpectedly little effect on tracheal morphogenesis. Structural analysis of mutant HS revealed not only a loss of corresponding sulfation, but also a compensatory increase of sulfation at other positions, which maintains the level of HS total charge. The restricted phenotypes of Hsst mutants are ascribed to this compensation because FGF signaling is strongly disrupted by Hs2st; Hs6st double mutation, or by overexpression of 6-O sulfatase, an extracellular enzyme which removes 6-O sulfate groups without increasing 2-O sulfation. These findings suggest that the overall sulfation level is more important than strictly defined HS fine structures for FGF signaling in some developmental contexts.

Citing Articles

In vivo activities of heparan sulfate differentially modified by NDSTs during development.

Nakato E, Baker S, Kinoshita-Toyoda A, Knudsen C, Lu Y, Takemura M Proteoglycan Res. 2024; 2(1).

PMID: 38616954 PMC: 11011245. DOI: 10.1002/pgr2.17.

Heparan-6--Endosulfatase 2 Promotes Invasiveness of Head and Neck Squamous Carcinoma Cell Lines in Co-Cultures with Cancer-Associated Fibroblasts.

Mukherjee P, Zhou X, Benicky J, Panigrahi A, Aljuhani R, Liu J Cancers (Basel). 2023; 15(21).

PMID: 37958342 PMC: 10650326. DOI: 10.3390/cancers15215168.

Structural Determinants of Substrate Recognition and Catalysis by Heparan Sulfate Sulfotransferases.

Gesteira T, Marforio T, Mueller J, Calvaresi M, Coulson-Thomas V ACS Catal. 2023; 11(17):10974-10987.

PMID: 37799563 PMC: 10550706. DOI: 10.1021/acscatal.1c03088.

Chondroitin sulfate is required for follicle epithelial integrity and organ shape maintenance in Drosophila.

Knudsen C, Woo Seuk Koh , Izumikawa T, Nakato E, Akiyama T, Kinoshita-Toyoda A Development. 2023; 150(17).

PMID: 37694610 PMC: 10508698. DOI: 10.1242/dev.201717.

VSIG4 interaction with heparan sulfates inhibits VSIG4-complement binding.

Ebstein S, Rafique A, Zhou Y, Krasco A, Montalvo-Ortiz W, Yu L Glycobiology. 2023; 33(7):591-604.

PMID: 37341346 PMC: 10426322. DOI: 10.1093/glycob/cwad050.

References

Toyoda H, Fox B, Selleck S . Structural analysis of glycosaminoglycans in animals bearing mutations in sugarless, sulfateless, and tout-velu. Drosophila homologues of vertebrate genes encoding glycosaminoglycan biosynthetic enzymes. J Biol Chem. 2000; 275(29):21856-61. DOI: 10.1074/jbc.M003540200. View

Jastrebova N, Vanwildemeersch M, Rapraeger A, Gimenez-Gallego G, Lindahl U, Spillmann D . Heparan sulfate-related oligosaccharides in ternary complex formation with fibroblast growth factors 1 and 2 and their receptors. J Biol Chem. 2006; 281(37):26884-92. DOI: 10.1074/jbc.M600806200. View

Schlessinger J, Plotnikov A, Ibrahimi O, Eliseenkova A, Yeh B, Yayon A . Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual role for heparin in FGFR binding and dimerization. Mol Cell. 2000; 6(3):743-50. DOI: 10.1016/s1097-2765(00)00073-3. View

Dhoot G, Gustafsson M, Ai X, Sun W, Standiford D, EMERSON Jr C . Regulation of Wnt signaling and embryo patterning by an extracellular sulfatase. Science. 2001; 293(5535):1663-6. DOI: 10.1126/science.293.5535.1663. View

Merry C, Bullock S, Swan D, Backen A, Lyon M, Beddington R . The molecular phenotype of heparan sulfate in the Hs2st-/- mutant mouse. J Biol Chem. 2001; 276(38):35429-34. DOI: 10.1074/jbc.M100379200. View

Sato M, Kornberg T . FGF is an essential mitogen and chemoattractant for the air sacs of the drosophila tracheal system. Dev Cell. 2002; 3(2):195-207. DOI: 10.1016/s1534-5807(02)00202-2. View

Nakato H, Kimata K . Heparan sulfate fine structure and specificity of proteoglycan functions. Biochim Biophys Acta. 2002; 1573(3):312-8. DOI: 10.1016/s0304-4165(02)00398-7. View

HajMohammadi S, Enjyoji K, Princivalle M, Christi P, Lech M, Beeler D . Normal levels of anticoagulant heparan sulfate are not essential for normal hemostasis. J Clin Invest. 2003; 111(7):989-99. PMC: 152578. DOI: 10.1172/JCI15809. View

Bulow H, Hobert O . Differential sulfations and epimerization define heparan sulfate specificity in nervous system development. Neuron. 2004; 41(5):723-36. DOI: 10.1016/s0896-6273(04)00084-4. View

10.

Kamimura K, Rhodes J, Ueda R, McNeely M, Shukla D, Kimata K . Regulation of Notch signaling by Drosophila heparan sulfate 3-O sulfotransferase. J Cell Biol. 2004; 166(7):1069-79. PMC: 2172002. DOI: 10.1083/jcb.200403077. View

11.

Habuchi H, Habuchi O, Kimata K . Sulfation pattern in glycosaminoglycan: does it have a code?. Glycoconj J. 2004; 21(1-2):47-52. DOI: 10.1023/B:GLYC.0000043747.87325.5e. View

12.

Klambt C, GLAZER L, Shilo B . breathless, a Drosophila FGF receptor homolog, is essential for migration of tracheal and specific midline glial cells. Genes Dev. 1992; 6(9):1668-78. DOI: 10.1101/gad.6.9.1668. View

13.

Chou T, Noll E, Perrimon N . Autosomal P[ovoD1] dominant female-sterile insertions in Drosophila and their use in generating germ-line chimeras. Development. 1993; 119(4):1359-69. DOI: 10.1242/dev.119.4.1359. View

14.

Sutherland D, Samakovlis C, Krasnow M . branchless encodes a Drosophila FGF homolog that controls tracheal cell migration and the pattern of branching. Cell. 1996; 87(6):1091-101. DOI: 10.1016/s0092-8674(00)81803-6. View

15.

Gabay L, Seger R, Shilo B . MAP kinase in situ activation atlas during Drosophila embryogenesis. Development. 1997; 124(18):3535-41. DOI: 10.1242/dev.124.18.3535. View

16.

Lin X, Buff E, Perrimon N, MICHELSON A . Heparan sulfate proteoglycans are essential for FGF receptor signaling during Drosophila embryonic development. Development. 1999; 126(17):3715-23. DOI: 10.1242/dev.126.17.3715. View

17.

Shukla D, Liu J, Blaiklock P, Shworak N, Bai X, Esko J . A novel role for 3-O-sulfated heparan sulfate in herpes simplex virus 1 entry. Cell. 1999; 99(1):13-22. DOI: 10.1016/s0092-8674(00)80058-6. View

18.

Kreuger J, Jemth P, Sanders-Lindberg E, Eliahu L, Ron D, Basilico C . Fibroblast growth factors share binding sites in heparan sulphate. Biochem J. 2005; 389(Pt 1):145-50. PMC: 1188264. DOI: 10.1042/BJ20042129. View

19.

Kennerdell J, Carthew R . Heritable gene silencing in Drosophila using double-stranded RNA. Nat Biotechnol. 2000; 18(8):896-8. DOI: 10.1038/78531. View