Neuropilin is a type I transmembrane protein initially identified by Takagi et al. (1987) as
an epitope recognized by a monoclonal antibody that labels specific subsets of axons in the developing Xenopus
nervous system. Neuropilin comprises in its extracellular domain several distinctive motifs; its cytoplasmic domain is
short (40 amino acids) and is highly conserved among Xenopus, mouse, and chick. He and Tessier-Lavigne (1997)
cloned the gene encoding human neuropilin and characterized the structure of the protein product.
Soker et al. (1998) described the purification and the expression cloning from tumor cells of a VEGF
receptor that binds VEGF165 but not VEGF121. This isoform-specific VEGF receptor (VEGF165R) is identical to
human neuropilin-1, which is also a receptor for the collapsin/semaphorin family that mediates neuronal cell guidance.
Soker et al. (1998) showed that when coexpressed in cells with KDR (VEGFR2; 191306), neuropilin-1 enhances the
binding of VEGF165 to KDR and VEGF165-mediated chemotaxis. Conversely, inhibition of VEGF165 binding to
neuropilin-1 inhibits its binding to KDR and its mitogenic activity for endothelial cells. They proposed
that neuropilin-1 is a novel VEGF receptor that modulates VEGF binding to KDR and subsequent bioactivity and
therefore may regulate VEGF-induced angiogenesis.
General function
Receptor
Comment
Cellular localization
Plasma membrane
Comment
Ovarian function
Comment
Changes in granulosa cells gene expression associated with increased oocyte competence in bovine. Nivet AL et al. One of the challenges in mammalian reproduction is to understand basic physiology of oocyte quality. It is believed that the follicle status is linked to developmental competence of the enclosed oocyte. To explore the link between follicles and competence in cows, a previous experiment from our laboratory has developed an ovarian stimulation protocol that increases and then decreases oocyte quality according to the timing of oocyte recovery post FSH withdrawal (coasting). Using such protocol, we have obtained the granulosa cells associated with oocytes of different qualities at selected times of coasting. Transcriptome analysis was done with Embryogene microarray slides and validation by real-time PCR. Results shows that the major changes in gene expression occurred from 20h to 44h of coasting, when oocyte quality rising. Secondly, among up-regulated genes (20h to 44h), 25%were extracellular molecules, highlighting potential granulosa signaling cascades. Principal component analysis identified 2 patterns: one resembling the competence profile and another associated with follicle growth and atresia. Additionally, 3 major functional changes were identified: 1) the end of follicle growth (BMPR1B, IGF2, RELN), involving interactions with the extracellular matrix (TFPI2); angiogenesis (NRP1), including early hypoxia, and potentially oxidative stress (GFPT2, TF, VNN1) and 2) apoptosis (KCNJ8) followed by 3) inflammation (ANKRD1). This unique window of analysis indicates a progressive hypoxia during coasting mixed with an increase of apoptosis and inflammation. Potential signaling pathways leading to competence have been identified and will require downstream testing. This preliminary analysis supports the potential role of the follicular differentiation in oocyte quality both during competence increase and decrease phases.
Expression regulated by
Steroids
Comment
Ovarian localization
Oocyte, Granulosa, Theca, Luteal cells
Comment
Hormonal regulation and differential expression of neuropilin (NRP)-1 and NRP-2 genes in bovine granulosa cells. Shimizu T et al. Although much is known about the biology of vascular endothelial growth factor (VEGF) and its receptors, little is known about the role of the VEGF receptors neuropilin (NRP)-1 and NRP-2 in the process of bovine follicle development. The aim of the present study was to examine the hormonal regulation of NRP-1 and NRP-2 mRNAs by real-time PCR in follicles from the bovine ovary and in cultured granulosa cells. The NRP-1 gene was expressed in the granulosa and theca cells in the post-selection (POF) and pre-selection (PRF) follicles in the bovine ovary. In contrast, the NRP-2 gene was expressed only in the theca cells in the POF and the PRF. The level of NRP-1 mRNA was significantly increased by treatment of the cultured granulosa cells with 10 ng/ml estradiol (E2). In contrast, the addition of progesterone (P4) to the culture medium decreased the expression of the NRP-1 gene. The level of NRP-1 mRNA was increased by 10 ng/ml E2 with or without 1 ng/ml P4, but the level of NRP-1 mRNA was decreased if the P4 level was increased to 10 ng/ml, even when 1 ng/ml E2 was also added. Follicle-stimulating hormone did not stimulate the expression of the NRP-1 gene. These results are the first data showing that NRP-1, but not NRP-2, is expressed in the granulosa cells of bovine follicles and that NRP-1 gene expression is regulated by sex steroids. Our findings suggest the involvement of NRP-1 in follicle development in the cow.
Neuropilin-1 and-2 expression in the monkey corpus luteum
during the menstrual cycle.
Author(s): Xu FH, Hazzard TM, Scheffler LJ, Stouffer RL
Source: BIOLOGY OF REPRODUCTION
v. 66(S1) pp. 181-182 2002 ABSTRACT