Eine Plattform für die Wissenschaft: Bauingenieurwesen, Architektur und Urbanistik
Eine Plattform für die Wissenschaft: Bauingenieurwesen, Architektur und Urbanistik
Role of Heparan sulfate in Indian Hedgehog signaling and Glycosaminoglycan composition ; Heparansulfate als Regulatoren von Indian Hedgehog und der Glykosaminoglykan Zusammensetzung
Indian hedgehog (Ihh), which belongs to the conserved family of Hedgehog proteins, is one of the key regulators of embryonic bone development. Several lines of evidence indicate that the distribution and activity of Ihh in the cartilage tissue are dependent on the extracellular matrix (ECM) composition and, particularly, on the level and sulfation pattern of Heparan sulfate (HS) (Dierker et al., 2016; Koziel et al., 2004; Ratzka et al., 2008; Yasuda et al., 2010). This work investigates the properties of the HS-Ihh interaction and the role of HS in the multimerization of Ihh. Moreover, the changes in GAG composition of mice with an altered HS structure were analyzed. In the closely related Sonic Hedgehog (Shh), two conserved HS-binding sequences, called Cardin-Weintraub (CW) motifs, which support a direct interaction with HS, have been proposed. (Chang et al., 2011; Farshi et al., 2011; Ohlig et al., 2011; Whalen et al., 2013). The current work demonstrates that Ihh, like Shh, also contains two CW motifs (CW1 and CW2). Both domains are highly conserved, but the CW1 sequence is not identical between Shh and Ihh. Mutation analysis revealed that the binding of Ihh, expressed in HEK-293Ebna cells to HS is mediated by both motifs, which, however, interact to specifically sulfated HS in distinct manners. Moreover, analysis of the Ihh multimerization showed that the CW1 and CW2 domains are essential, but–correlating with their HS affinity–distinctly important for multimer formation. Surprisingly, analysis of the role of the HS modification pattern on the binding affinity of Shh and Ihh showed that loss of N-sulfation leads to an increased affinity of both proteins. 2-Osulfate deficient HS bound Ihh with similar, but Shh with higher affinity than wild type HS. To better understand how the differences between the Shh and Ihh CW1 sequences impact their HS binding, the affinities of the two paralogs to HS were compared. By exchanging the HS-interacting regions, this work demonstrates that these variations result in ...
Role of Heparan sulfate in Indian Hedgehog signaling and Glycosaminoglycan composition ; Heparansulfate als Regulatoren von Indian Hedgehog und der Glykosaminoglykan Zusammensetzung
Indian hedgehog (Ihh), which belongs to the conserved family of Hedgehog proteins, is one of the key regulators of embryonic bone development. Several lines of evidence indicate that the distribution and activity of Ihh in the cartilage tissue are dependent on the extracellular matrix (ECM) composition and, particularly, on the level and sulfation pattern of Heparan sulfate (HS) (Dierker et al., 2016; Koziel et al., 2004; Ratzka et al., 2008; Yasuda et al., 2010). This work investigates the properties of the HS-Ihh interaction and the role of HS in the multimerization of Ihh. Moreover, the changes in GAG composition of mice with an altered HS structure were analyzed. In the closely related Sonic Hedgehog (Shh), two conserved HS-binding sequences, called Cardin-Weintraub (CW) motifs, which support a direct interaction with HS, have been proposed. (Chang et al., 2011; Farshi et al., 2011; Ohlig et al., 2011; Whalen et al., 2013). The current work demonstrates that Ihh, like Shh, also contains two CW motifs (CW1 and CW2). Both domains are highly conserved, but the CW1 sequence is not identical between Shh and Ihh. Mutation analysis revealed that the binding of Ihh, expressed in HEK-293Ebna cells to HS is mediated by both motifs, which, however, interact to specifically sulfated HS in distinct manners. Moreover, analysis of the Ihh multimerization showed that the CW1 and CW2 domains are essential, but–correlating with their HS affinity–distinctly important for multimer formation. Surprisingly, analysis of the role of the HS modification pattern on the binding affinity of Shh and Ihh showed that loss of N-sulfation leads to an increased affinity of both proteins. 2-Osulfate deficient HS bound Ihh with similar, but Shh with higher affinity than wild type HS. To better understand how the differences between the Shh and Ihh CW1 sequences impact their HS binding, the affinities of the two paralogs to HS were compared. By exchanging the HS-interacting regions, this work demonstrates that these variations result in ...
Role of Heparan sulfate in Indian Hedgehog signaling and Glycosaminoglycan composition ; Heparansulfate als Regulatoren von Indian Hedgehog und der Glykosaminoglykan Zusammensetzung
Bachvarova, Velina Dimitrova (Autor:in) / Vortkamp, Andrea
26.03.2024
Hochschulschrift
Elektronische Ressource
Englisch
The Hedgehog Signaling Network
| British Library Conference Proceedings | 2003
Nerves Control Redox Levels in Mature Tissues Through Schwann Cells and Hedgehog Signaling
British Library Online Contents | 2016
ZnO hedgehog-like structures for control cell cultivation
| British Library Online Contents | 2012
| Wiley | 2024
| Wiley | 2024