Secreted class 3 semaphorins (Sema3), which signal through holoreceptor complexes that are formed by different subunits, such as neuropilins (Nrps), proteoglycans, and plexins, were initially characterized as fundamental regulators of axon guidance during embryogenesis. Subsequently, Sema3A, Sema3C, Sema3D, and Sema3E were discovered to play crucial roles in cardiovascular development, mainly acting through Nrp1 and Plexin D1, which funnels the signal of multiple Sema3 in vascular endothelial cells. Mechanistically, Sema3 proteins control cardiovascular patterning through the enzymatic GTPase-activating-protein activity of the cytodomain of Plexin D1, which negatively regulates the function of Rap1, a small GTPase that is well-known for its ability to drive vascular morphogenesis and to elicit the conformational activation of integrin adhesion receptors.

Class 3 semaphorins in cardiovascular development

VALDEMBRI, Donatella;REGANO, DONATELLA;MAIONE, FEDERICA;GIRAUDO, Enrico;SERINI, Guido
Last
2016-01-01

Abstract

Secreted class 3 semaphorins (Sema3), which signal through holoreceptor complexes that are formed by different subunits, such as neuropilins (Nrps), proteoglycans, and plexins, were initially characterized as fundamental regulators of axon guidance during embryogenesis. Subsequently, Sema3A, Sema3C, Sema3D, and Sema3E were discovered to play crucial roles in cardiovascular development, mainly acting through Nrp1 and Plexin D1, which funnels the signal of multiple Sema3 in vascular endothelial cells. Mechanistically, Sema3 proteins control cardiovascular patterning through the enzymatic GTPase-activating-protein activity of the cytodomain of Plexin D1, which negatively regulates the function of Rap1, a small GTPase that is well-known for its ability to drive vascular morphogenesis and to elicit the conformational activation of integrin adhesion receptors.
2016
10
6
641
651
Valdembri, Donatella; Regano, Donatella; Maione, Federica; Giraudo, Enrico; Serini, Guido
File in questo prodotto:
File Dimensione Formato  
Valdembri et al_CAM_2016.pdf

Accesso aperto

Tipo di file: POSTPRINT (VERSIONE FINALE DELL’AUTORE)
Dimensione 391.09 kB
Formato Adobe PDF
391.09 kB Adobe PDF Visualizza/Apri
kcam-10-06-1212805.pdf

Accesso riservato

Tipo di file: PDF EDITORIALE
Dimensione 540.36 kB
Formato Adobe PDF
540.36 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1593768
Citazioni
  • ???jsp.display-item.citation.pmc??? 15
  • Scopus 39
  • ???jsp.display-item.citation.isi??? 37
social impact