Molecular mechanisms of proteoglycan- mediated semaphorin
signaling in axon guidance

J 2024

Molecular mechanisms of proteoglycan- mediated semaphorin signaling in axon guidance

NOURISANAMI, Farahdokht; Margarita SOBOL; Zhuoran LI; Matej HORVATH; Karolina KOWALSKA et. al.

Basic information

Original name

Molecular mechanisms of proteoglycan- mediated semaphorin signaling in axon guidance

Authors

NOURISANAMI, Farahdokht; Margarita SOBOL; Zhuoran LI; Matej HORVATH; Karolina KOWALSKA; Atul KUMAR; Jonas VLASAK; Nicola KOUPILOVA; David J LUGINBUHL; Liqun LUO and Daniel ROZBESKY

Edition

Proceedings of the National Academy of Sciences of the United States of America, WASHINGTON, National Academy of Sciences, 2024, 0027-8424

Other information

Language

English

Type of outcome

Article in a journal

Field of Study

30103 Neurosciences

Country of publisher

United States of America

Confidentiality degree

is not subject to a state or trade secret

References:

URL

Impact factor

Impact factor: 9.100

RIV identification code

RIV/00216224:90127/24:00139058

DOI

https://doi.org/10.1073/pnas.2402755121

UT WoS

001397018400015

EID Scopus

2-s2.0-85200152595

Keywords in English

semaphorin; semaphorin bridge model; glycosaminoglycans; axon guidance; Sema2b

Abstract

In the original language

The precise assembly of a functional nervous system relies on axon guidance cues. Beyond engaging their cognate receptors and initiating signaling cascades that modulate cytoskeletal dynamics, guidance cues also bind components of the extracellular matrix, notably proteoglycans, yet the role and mechanisms of these interactions remain poorly understood. We found that Drosophila secreted semaphorins bind specifically to glycosaminoglycan (GAG) chains of proteoglycans, showing a preference based on the degree of sulfation. Structural analysis of Sema2b unveiled multiple GAG- binding sites positioned outside canonical plexin- binding site, with the highest affinity binding site located at the C- terminal tail, characterized by a lysine- rich helical arrangement that appears to be conserved across secreted semaphorins. In vivo studies revealed a crucial role of the Sema2b C- terminal tail in specifying the trajectory of olfactory receptor neurons. We propose that secreted semaphorins tether to the cell surface through interactions with GAG chains of proteoglycans, facilitating their presentation to cognate receptors on passing axons.

Links

90242, large research infrastructures

Name: CIISB III

90250, large research infrastructures

Name: Czech-BioImaging III

90254, large research infrastructures

Name: e-INFRA CZ II

Cite

NOURISANAMI, Farahdokht; Margarita SOBOL; Zhuoran LI; Matej HORVATH; Karolina KOWALSKA; Atul KUMAR; Jonas VLASAK; Nicola KOUPILOVA; David J LUGINBUHL; Liqun LUO and Daniel ROZBESKY. Molecular mechanisms of proteoglycan- mediated semaphorin signaling in axon guidance. Proceedings of the National Academy of Sciences of the United States of America. WASHINGTON: National Academy of Sciences, 2024, vol. 121, No 31, p. 1-10. ISSN 0027-8424. Available from: https://doi.org/10.1073/pnas.2402755121.

@article{2483883,
   author = {Nourisanami, Farahdokht and Sobol, Margarita and Li, Zhuoran and Horvath, Matej and Kowalska, Karolina and Kumar, Atul and Vlasak, Jonas and Koupilova, Nicola and Luginbuhl, David J and Luo, Liqun and Rozbesky, Daniel},
   article_location = {WASHINGTON},
   article_number = {31},
   doi = {https://doi.org/10.1073/pnas.2402755121},
   keywords = {semaphorin; semaphorin bridge model; glycosaminoglycans; axon guidance; Sema2b},
   language = {eng},
   issn = {0027-8424},
   journal = {Proceedings of the National Academy of Sciences of the United States of America},
   title = {Molecular mechanisms of proteoglycan- mediated semaphorin signaling in axon guidance},
   url = {https://www.pnas.org/doi/10.1073/pnas.2402755121},
   volume = {121},
   year = {2024}
}

TY  - JOUR
ID  - 2483883
AU  - Nourisanami, Farahdokht - Sobol, Margarita - Li, Zhuoran - Horvath, Matej - Kowalska, Karolina - Kumar, Atul - Vlasak, Jonas - Koupilova, Nicola - Luginbuhl, David J - Luo, Liqun - Rozbesky, Daniel
PY  - 2024
TI  - Molecular mechanisms of proteoglycan- mediated semaphorin signaling in axon guidance
JF  - Proceedings of the National Academy of Sciences of the United States of America
VL  - 121
IS  - 31
SP  - 1-10
EP  - 1-10
PB  - National Academy of Sciences
SN  - 00278424
KW  - semaphorin
KW  - semaphorin bridge model
KW  - glycosaminoglycans
KW  - axon guidance
KW  - Sema2b
UR  - https://www.pnas.org/doi/10.1073/pnas.2402755121
N2  - The precise assembly of a functional nervous system relies on axon guidance cues. Beyond engaging their cognate receptors and initiating signaling cascades that modulate cytoskeletal dynamics, guidance cues also bind components of the extracellular matrix, notably proteoglycans, yet the role and mechanisms of these interactions remain poorly understood. We found that Drosophila secreted semaphorins bind specifically to glycosaminoglycan (GAG) chains of proteoglycans, showing a preference based on the degree of sulfation. Structural analysis of Sema2b unveiled multiple GAG- binding sites positioned outside canonical plexin- binding site, with the highest affinity binding site located at the C- terminal tail, characterized by a lysine- rich helical arrangement that appears to be conserved across secreted semaphorins. In vivo studies revealed a crucial role of the Sema2b C- terminal tail in specifying the trajectory of olfactory receptor neurons. We propose that secreted semaphorins tether to the cell surface through interactions with GAG chains of proteoglycans, facilitating their presentation to cognate receptors on passing axons.
ER  -

NOURISANAMI, Farahdokht; Margarita SOBOL; Zhuoran LI; Matej HORVATH; Karolina KOWALSKA; Atul KUMAR; Jonas VLASAK; Nicola KOUPILOVA; David J LUGINBUHL; Liqun LUO and Daniel ROZBESKY. Molecular mechanisms of proteoglycan- mediated semaphorin signaling in axon guidance. \textit{Proceedings of the National Academy of Sciences of the United States of America}. WASHINGTON: National Academy of Sciences, 2024, vol.~121, No~31, p.~1-10. ISSN~0027-8424. Available from: https://doi.org/10.1073/pnas.2402755121.

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