Molecular mechanisms of proteoglycan-mediated semaphorin signaling in axon guidance.

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F24%3A00604436" target="_blank" >RIV/68378050:_____/24:00604436 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/24:10489568 RIV/00216224:90127/24:00139058

Výsledek na webu

<a href="https://www.pnas.org/doi/epdf/10.1073/pnas.2402755121" target="_blank" >https://www.pnas.org/doi/epdf/10.1073/pnas.2402755121</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1073/pnas.2402755121" target="_blank" >10.1073/pnas.2402755121</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Molecular mechanisms of proteoglycan-mediated semaphorin signaling in axon guidance.

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Molecular mechanisms of proteoglycan-mediated semaphorin signaling in axon guidance.

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Proceedings of the National Academy of Sciences of the United States of America

ISSN

0027-8424

e-ISSN

1091-6490

Svazek periodika

121

Číslo periodika v rámci svazku

31

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

"e2402755121"

Kód UT WoS článku

001397018400015

EID výsledku v databázi Scopus

2-s2.0-85200152595