טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentShraga-Heled Niva
SubjectCharacterization of the Role of Semaphorin-3F in
Endothellal Cells
DepartmentDepartment of Biology
Supervisor Professor Emeritus Gera Neufeld


Abstract

Neuropilins function as receptors for the axon guidance factors belonging to the class-3 semaphorin subfamily. Class-3 semaphorins cause depolimerization of the actin cytoskeleton at the growing tips of axons and direct the growth of the tip of the axon in this fashion. Neuropilins were also found to be expressed by endothelial cells and to bind vascular endothelial growth factor (VEGF165). In this work we show that semaphorin 3F affects endothelial cells in a manner that resembles its effect on axonal growth cones.

The neuropilins are thought to function as co-receptors that form functional signaling receptors by associating with trans-membrane proteins such as the class-A plexins. The functional receptor for semaphorin-3F consists of a complex of neuropilin-2 and either plexin-A1 or plexin-A2.

We found that semaphorin-3F can cause the contraction of porcine aortic endothelial (PAE) cells co-expressing recombinant neuropilin-2 and plexin-A1. Semaphorin-3F also induces contraction of primary umbilical vein derived endothelial  (HUE) cells which express neuropilin-2, neuropilin-1, plexin-A1 and plexin-A2. Semaphorin-3F was also found to inhibit the endothelial sprouting induced by a mixture of fibroblast growth factor (FGF) and VEGF165 from HUE spheroids. This result suggests that semaphorin-3F can interfere with VEGF165 and FGF induced angiogenesis, either through competition with VEGF165 or through a FGF and VEGF independent pathway leading to actin depolimerization.

 I also found that Semaphorin-3A and semaphorin-3F are expressed by several tumor derived cell lines and by primary artery and vein derived endothelial cells.