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Donatella Valdembri1,2, Donatella Regano3,4, Federica Maione3,4

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Secreted class 3 semaphorins (Sema3) regulate cardiovascular development by controlling vascular endothelial cell signaling. They modulate Rap1 GTPase activity via Plexin D1, impacting vascular morphogenesis and integrin activation.

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Area of Science:

  • Cardiovascular Biology
  • Developmental Biology
  • Cell Signaling

Background:

  • Secreted class 3 semaphorins (Sema3) are key regulators of axon guidance.
  • Sema3 family members, including Sema3A, C, D, and E, are crucial for cardiovascular development.
  • Vascular endothelial cells utilize neuropilin 1 (Nrp1) and Plexin D1 (PlxnD1) to receive Sema3 signals.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which Sema3 proteins influence cardiovascular patterning.
  • To investigate the role of Plexin D1 signaling in vascular endothelial cells.

Main Methods:

  • Analysis of Sema3 signaling pathways in vascular endothelial cells.
  • Investigating the interaction between Sema3, Nrp1, PlxnD1, and Rap1.
  • Studying the GTPase-activating protein (GAP) activity of PlxnD1's cytodomain.

Main Results:

  • Sema3 proteins signal through Nrp1 and PlxnD1 complexes in vascular endothelial cells.
  • PlxnD1's cytodomain possesses GTPase-activating protein activity.
  • This activity negatively regulates Rap1, a GTPase involved in vascular morphogenesis and integrin activation.

Conclusions:

  • Sema3 signaling, mediated by Nrp1 and PlxnD1, is critical for cardiovascular development.
  • Plexin D1 acts as a signaling hub, controlling Rap1 activity to regulate vascular patterning.
  • Understanding this pathway offers insights into vascular morphogenesis and integrin function.