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Structure and functional relevance of the Slit2 homodimerization domain
Author(s) -
Seiradake Elena,
von Philipsborn Anne C,
Henry Maud,
Fritz Martin,
LortatJacob Hugues,
Jamin Marc,
Hemrika Wieger,
Bastmeyer Martin,
Cusack Stephen,
McCarthy Andrew A
Publication year - 2009
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2009.95
Subject(s) - slit , axon guidance , growth cone , microbiology and biotechnology , lamellipodium , roundabout , receptor , heparan sulfate , chemistry , axon , biology , biochemistry , cell , cell migration , neuroscience
Slit proteins are secreted ligands that interact with the Roundabout (Robo) receptors to provide important guidance cues in neuronal and vascular development. Slit–Robo signalling is mediated by an interaction between the second Slit domain and the first Robo domain, as well as being dependent on heparan sulphate. In an effort to understand the role of the other Slit domains in signalling, we determined the crystal structure of the fourth Slit2 domain (D4) and examined the effects of various Slit2 constructs on chick retinal ganglion cell axons. Slit2 D4 forms a homodimer using the conserved residues on its concave face, and can also bind to heparan sulphate. We observed that Slit2 D4 frequently results in growth cones with collapsed lamellipodia and that this effect can be inhibited by exogenously added heparan sulphate. Our results show that Slit2 D4–heparan sulphate binding contributes to a Slit–Robo signalling mechanism more intricate than previously thought.