Advertisement

Emerging Roles of Heparan Sulfate in Axon Guidance Signaling

  • Masayuki Masu
Chapter

Abstract

Accurate wiring of the neural network is a fundamental for higher brain functions. In the developing brain, growing axons are navigated towards their targets by the concerted actions of chemoattractants and chemorepellents. Recent studies have revealed that heparan sulfate, a glycosaminoglycan sugar chain attached to core proteins in proteoglycans, plays pivotal roles in regulating axon guidance signaling. Here some of the topics related to heparan sulfate in axon guidance are reviewed with emphasis on its structure and activity in relation to its synthesizing and modifying enzymes.

Keywords

Autism Spectrum Disorder Heparan Sulfate Axon Guidance Sugar Chain Heparan Sulfate Chain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

BMP

Bone morphogenetic protein

DCC

Deleted in colorectal cancer

FGF

Fibroblast growth factor

GDNF

Glial cell line-derived neurotrophic factor

GlcA

Glucuronic acid

GlcNAc

N-acetylglucosamine

HB-EGF

Heparin-binding epidermal growth factor

HGF

Hepatocyte growth factor

HS

Heparan sulfate

HSPG

Heparan sulfate proteoglycans

IdoA

Iduronic acid

Shh

Sonic hedgehog

TGFβ

Transforming growth factor-β

VEGF

Vascular endothelial growth factor

References

  1. Ai X, Do AT, Lozynska O, Kusche-Gullberg M, Lindahl U, Emerson CP Jr (2003) QSulf1 remodels the 6-O-sulfation states of cell surface heparan sulfate proteoglycans to promote Wnt signaling. J Cell Biol 162:341–351PubMedCrossRefGoogle Scholar
  2. Bülow HE, Hobert O (2004) Differential sulfations and epimerization define heparan sulfate specificity in nervous system development. Neuron 41:723–736PubMedCrossRefGoogle Scholar
  3. Bülow HE, Hobert O (2006) The molecular diversity of glycosaminoglycans shapes animal development. Annu Rev Cell Dev Biol 22:375–407PubMedCrossRefGoogle Scholar
  4. Charron F, Tessier-Lavigne M (2005) Novel brain wiring functions for classical morphogens: a role as graded positional cues in axon guidance. Development 132:2251–2262PubMedCrossRefGoogle Scholar
  5. Dhoot GK, Gustafsson MK, Ai X, Sun W, Standiford DM, Emerson CP Jr (2001) Regulation of Wnt signaling and embryo patterning by an extracellular sulfatase. Science 293:1663–1666PubMedCrossRefGoogle Scholar
  6. Dickson BJ, Zou Y (2010) Navigating intermediate targets: the nervous system midline. Cold Spring Harb Perspect Biol 2:a002055PubMedCrossRefGoogle Scholar
  7. Esko JD, Selleck SB (2002) Order out of chaos: assembly of ligand binding sites in heparan sulfate. Annu Rev Biochem 71:435–471PubMedCrossRefGoogle Scholar
  8. Holst CR, Bou-Reslan H, Gore BB, Wong K, Grant D, Chalasani S, Carano RA, Frantz GD, Tessier-Lavigne M, Bolon B, French DM, Ashkenazi A (2007) Secreted sulfatases Sulf1 and Sulf2 have overlapping yet essential roles in mouse neonatal survival. PLoS One 2:e575PubMedCrossRefGoogle Scholar
  9. Holt CE, Dickson BJ (2005) Sugar codes for axons? Neuron 46:169–172PubMedCrossRefGoogle Scholar
  10. Inatani M, Irie F, Plump AS, Tessier-Lavigne M, Yamaguchi Y (2003) Mammalian brain morphogenesis and midline axon guidance require heparan sulfate. Science 302:1044–1046PubMedCrossRefGoogle Scholar
  11. Kantor DB, Chivatakarn O, Peer KL, Oster SF, Inatani M, Hansen MJ, Flanagan JG, Yamaguchi Y, Sretavan DW, Giger RJ, Kolodkin AL (2004) Semaphorin 5A is a bifunctional axon guidance cue regulated by heparan and chondroitin sulfate proteoglycans. Neuron 44:961–975PubMedCrossRefGoogle Scholar
  12. Karlstrom RO, Trowe T, Klostermann S, Baier H, Brand M, Crawford AD, Grunewald B, Haffter P, Hoffmann H, Meyer SU, Muller BK, Richter S, van Eeden FJ, Nusslein-Volhard C, Bonhoeffer F (1996) Zebrafish mutations affecting retinotectal axon pathfinding. Development 123:427–438PubMedGoogle Scholar
  13. Kolodkin AL, Tessier-Lavigne M (2011) Mechanisms and molecules of neuronal wiring: a primer. Cold Spring Harb Perspect Biol 3:a001727PubMedCrossRefGoogle Scholar
  14. Lamanna WC, Baldwin RJ, Padva M, Kalus I, Ten Dam G, van Kuppevelt TH, Gallagher JT, von Figura K, Dierks T, Merry CL (2006) Heparan sulfate 6-O-endosulfatases: discrete in vivo activities and functional co-operativity. Biochem J 400:63–73PubMedCrossRefGoogle Scholar
  15. Lamanna WC, Kalus I, Padva M, Baldwin RJ, Merry CL, Dierks T (2007) The heparanome–the enigma of encoding and decoding heparan sulfate sulfation. J Biotechnol 129:290–307PubMedCrossRefGoogle Scholar
  16. Langsdorf A, Do AT, Kusche-Gullberg M, Emerson CP Jr, Ai X (2007) Sulfs are regulators of growth factor signaling for satellite cell differentiation and muscle regeneration. Dev Biol 311:464–477PubMedCrossRefGoogle Scholar
  17. Lee JS, Chien CB (2004) When sugars guide axons: insights from heparan sulphate proteoglycan mutants. Nat Rev Genet 5:923–935PubMedCrossRefGoogle Scholar
  18. Lee JS, von der Hardt S, Rusch MA, Stringer SE, Stickney HL, Talbot WS, Geisler R, Nusslein-Volhard C, Selleck SB, Chien CB, Roehl H (2004) Axon sorting in the optic tract requires HSPG synthesis by ext2 (dackel) and extl3 (boxer). Neuron 44:947–960PubMedCrossRefGoogle Scholar
  19. Lin X (2004) Functions of heparan sulfate proteoglycans in cell signaling during development. Development 131:6009–6021PubMedCrossRefGoogle Scholar
  20. Lindahl U, Kusche-Gullberg M, Kjellen L (1998) Regulated diversity of heparan sulfate. J Biol Chem 273:24979–24982PubMedCrossRefGoogle Scholar
  21. Matsumoto Y, Irie F, Inatani M, Tessier-Lavigne M, Yamaguchi Y (2007) Netrin-1/DCC signaling in commissural axon guidance requires cell-autonomous expression of heparan sulfate. J Neurosci 27:4342–4350PubMedCrossRefGoogle Scholar
  22. Morimoto-Tomita M, Uchimura K, Werb Z, Hemmerich S, Rosen SD (2002) Cloning and characterization of two extracellular heparin-degrading endosulfatases in mice and humans. J Biol Chem 277:49175–49185PubMedCrossRefGoogle Scholar
  23. Nagamine S, Koike S, Keino-Masu K, Masu M (2005) Expression of a heparan sulfate remodeling enzyme, heparan sulfate 6-O-endosulfatase sulfatase FP2, in the rat nervous system. Brain Res Dev Brain Res 159:135–143PubMedCrossRefGoogle Scholar
  24. Nagamine S, Tamba M, Ishimine H, Araki K, Shiomi K, Okada T, Ohto T, Kunita S, Takahashi S, Wismans RG, van Kuppevelt TH, Masu M, Keino-Masu K (2012) Organ-specific sulfation patterns of heparan sulfate generated by extracellular sulfatases Sulf1 and Sulf2 in mice. J Biol Chem 287:9579–9590PubMedCrossRefGoogle Scholar
  25. Ohto T, Uchida H, Yamazaki H, Keino-Masu K, Matsui A, Masu M (2002) Identification of a novel nonlysosomal sulphatase expressed in the floor plate, choroid plexus and cartilage. Genes Cells 7:173–185PubMedCrossRefGoogle Scholar
  26. Parenti G, Meroni G, Ballabio A (1997) The sulfatase gene family. Curr Opin Genet Dev 7:386–391PubMedCrossRefGoogle Scholar
  27. Perrimon N, Bernfield M (2000) Specificities of heparan sulphate proteoglycans in developmental processes. Nature 404:725–728PubMedCrossRefGoogle Scholar
  28. Pratt T, Conway CD, Tian NM, Price DJ, Mason JO (2006) Heparan sulphation patterns generated by specific heparan sulfotransferase enzymes direct distinct aspects of retinal axon guidance at the optic chiasm. J Neurosci 26:6911–6923PubMedCrossRefGoogle Scholar
  29. Ratzka A, Kalus I, Moser M, Dierks T, Mundlos S, Vortkamp A (2008) Redundant function of the heparan sulfate 6-O-endosulfatases Sulf1 and Sulf2 during skeletal development. Dev Dyn 237:339–353PubMedCrossRefGoogle Scholar
  30. Uchimura K, Morimoto-Tomita M, Bistrup A, Li J, Lyon M, Gallagher J, Werb Z, Rosen SD (2006) HSulf-2, an extracellular endoglucosamine-6-sulfatase, selectively mobilizes heparin-bound growth factors and chemokines: effects on VEGF, FGF-1, and SDF-1. BMC Biochem 7:2PubMedCrossRefGoogle Scholar
  31. Van Vactor D, Wall DP, Johnson KG (2006) Heparan sulfate proteoglycans and the emergence of neuronal connectivity. Curr Opin Neurobiol 16:40–51PubMedCrossRefGoogle Scholar
  32. Viviano BL, Paine-Saunders S, Gasiunas N, Gallagher J, Saunders S (2004) Domain-specific modification of heparan sulfate by Qsulf1 modulates the binding of the bone morphogenetic protein antagonist Noggin. J Biol Chem 279:5604–5611PubMedCrossRefGoogle Scholar
  33. Wang S, Ai X, Freeman SD, Pownall ME, Lu Q, Kessler DS, Emerson CP Jr (2004) QSulf1, a heparan sulfate 6-O-endosulfatase, inhibits fibroblast growth factor signaling in mesoderm induction and angiogenesis. Proc Natl Acad Sci U S A 101:4833–4838PubMedCrossRefGoogle Scholar
  34. Yu TW, Bargmann CI (2001) Dynamic regulation of axon guidance. Nat Neurosci 4(Suppl):1169–1176PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2013

Authors and Affiliations

  1. 1.Department of Molecular NeurobiologyUniversity of TsukubaTsukubaJapan

Personalised recommendations