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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Biol+Chem
2014 ; 289
(26
): 17971-9
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Semaphorin 3d and semaphorin 3e direct endothelial motility through distinct
molecular signaling pathways
#MMPMID24825896
Aghajanian H
; Choi C
; Ho VC
; Gupta M
; Singh MK
; Epstein JA
J Biol Chem
2014[Jun]; 289
(26
): 17971-9
PMID24825896
show ga
Class 3 semaphorins were initially described as axonal growth cone guidance
molecules that signal through plexin and neuropilin coreceptors and since then
have been established to be regulators of vascular development. Semaphorin 3e
(Sema3e) has been shown previously to repel endothelial cells and is the only
class 3 semaphorin known to be capable of signaling via a plexin receptor without
a neuropilin coreceptor. Sema3e signals through plexin D1 (Plxnd1) to regulate
vascular patterning by modulating the cytoskeleton and focal adhesion structures.
We showed recently that semaphorin 3d (Sema3d) mediates endothelial cell
repulsion and pulmonary vein patterning during embryogenesis. Here we show that
Sema3d and Sema3e affect human umbilical vein endothelial cells similarly but
through distinct molecular signaling pathways. Time-lapse imaging studies show
that both Sema3d and Sema3e can inhibit cell motility and migration, and tube
formation assays indicate that both can impede tubulogenesis. Endothelial cells
incubated with either Sema3d or Sema3e demonstrate a loss of actin stress fibers
and focal adhesions. However, the addition of neuropilin 1 (Nrp1)-blocking
antibody or siRNA knockdown of Nrp1 inhibits Sema3d-mediated, but not
Sema3e-mediated, cytoskeletal reorganization, and siRNA knockdown of Nrp1
abrogates Sema3d-mediated, but not Sema3e-mediated, inhibition of tubulogenesis.
On the other hand, endothelial cells deficient in Plxnd1 are resistant to
endothelial repulsion mediated by Sema3e but not Sema3d. Unlike Sema3e, Sema3d
incubation results in phosphorylation of Akt in human umbilical vein endothelial
cells, and inhibition of the PI3K/Akt pathway blocks the endothelial guidance and
cytoskeletal reorganization functions of Sema3d but not Sema3e.