SynonymsBot
Synonyms for netrin or Related words with netrin
neogenin
plexin
neuropilins
netrins
neuropilin
norrin
rgmb
sorla
semaphorin
agrin
sortilin
tgfrii
neuregulins
ephrin
semaphorins
bmpr
sfrps
hevin
misrii
neurofascin
trii
nogo
tgfbeta
pirb
pleiotrophin
vegfd
syndecan
endodomain
sost
opticin
glypican
nucleostemin
synaptogenic
wnts
sclerostin
ephrinb
rgma
notum
rhamm
tweakr
rhogtpase
trkc
ngr
caspr
dickkopf
noggin
sprouty
mimecan
epor
nrtn
Examples of "netrin"
Netrin
is included in a family of laminin-related secreted proteins. The function of this gene has not yet been defined; however,
netrin
is thought to be involved in axon guidance and cell migration during development. Mutations and loss of expression of
netrin
suggest that variation in
netrin
may be involved in cancer development.
Netrin
repulsion can also be mediated by changes in cyclic nucleotide levels;
Netrin
-1 induces a repulsive response when cAMP signaling is inhibited.
Netrin
-1 gradient in "Xenopus laevis" ganglion cell can induce turning of retinal growth cones "in vitro" to steer axons out of the retina.
Netrin
(unc-6, "Caenorhabditis elegans" homologue) and its corresponding receptor DCC (Deleted in Colorectal Cancer) were initially identified as an attractive interaction. DCC, expressed by commissural axons, binds to
Netrin
with high affinity; inhibiting
Netrin
/DCC signaling interferes with the attractive turning of retinal growth cones.
In adults,
netrin
has been implicated in the regulation of stem cell movement and inflammation.
Netrin
1 has been found to inhibit leukocyte migration to inflamed areas in the body. This provides evidence that the up regulation of
netrin
protects injured tissue from excess inflammation. Also, the migration of adult neural progenitor cell and adult spinal cord progenitor cells to the spine is
netrin
1 dependent. Little is known behind the mechanism regarding the inhibition or attraction of these stem cells.
Netrin
-3 is different from other netrins. While expressed during development of the peripheral nervous system in the motor, sensory and sympathetic neurons, it is very limited in the central nervous system. Studies with
netrin
-3 have noticed a reduced ability to bind with DCC when compared with
netrin
-1. This suggests that it mainly operates through other receptors.
There are still many unanswered questions regarding the
netrin
family of molecules. It is still unsure what role vertebrate homologues of UNC-5 play in chemorepulsion. Although much is known about the expression of
netrin
during development, little is still known about its regulation in later development in the brain.
Netrin
knockout mice show that there is much to learn about the many roles of
netrin
in axonal guidance.
Netrin
has been implicated as a vital molecule for the proliferation of vascular networks. Multiple studies have found different effects of
netrin
on these branching vessels. The endothelial tip cells in vascular tissue display similar properties to the growth cone found in neuronal tissue. Studies have discovered that these same endothelial tip cells also express UNC5B, which
netrin
1 can bind to, inhibiting angiogenesis. In contrast, several studies show that
netrin
-1 actually promotes blood vessel branching. In conjunction with this research, it has been found that
netrin
4 is responsible for growth in the lymphatic vascular system. Overall, these studies show that regulating effects of
netrin
is dependent on the type of vascular tissue. Recently,
netrin
has been implicated in angiogenesis in the placenta, making it vital to the survival of the fetus. This finding has implications in the future treatment of vascular disease in the placenta.
. For example,
netrin
-1 is both a chemoattractant and a chemorepellent for many classes of axons, and her 1997 study shows that the growth cone of spinal neurons is chemoattractive to
netrin
-1 yet chemorepulsive when cAMP is present. Therefore, the presence of
netrin
-1 may serve as a cue for axonal growth. Further studies have also found that
netrin
receptor DCC and laminin-1 are other factors related to
netrin
-1 work in axon guidance. Christine also currently collaborates with Giovanni Armenise-Harvard laboratory of axonal neurobiology
Studies in "C. elegans" revealed a possible mechanism for
Netrin
acting as a chemorepulsive agent (). Unc-5, a transmembrane protein, is required for dorsal migration of axons in nematodes; it was determined that unc-5 acts as a repulsive receptor for
Netrin
(unc-6). The switch between attractive and repulsive
Netrin
signaling can be mediated by misexpression of unc-5 in commissural axons.
Netrin
-1/DCC binding induces DCC homodimerization leading to an attractive response; on the other hand, the chemorepellent response is triggered via
Netrin
-1 binding to unc-5/DCC heterodimers.
DCC and neogenin, two of the
netrin
-1 receptors, have recently been shown to have sites for tyrosine phosphorylation (at Y1420 on DCC) and are likely interacting with Src family kinases in regulating responses to
netrin
-1.
In various human cancers, it has been shown that
netrin
becomes over-expressed. In conjunction, it has been shown that certain receptors become down-regulated in this process. The
netrin
receptors DCC and UNC5H are responsible for apoptotic regulation. The absence of
netrin
1 is responsible for apoptosis, while the presence of
netrin
1 leads to an inhibition of the apoptosis pathway. This pathway is unique and independent of the mitochondrial and death receptor pathways that lead to controlled cell death. This has been observed in the human colon epithelium, where higher levels of natural cell death at the upper portion of the villi correlated with a smaller gradient of
netrin
-1. This correlated the role of
netrin
with tissue death and growth. Tumor suppressor p53 is responsible for the expression of the
netrin
-1, implicating that
netrin
may be the pathway through which p53 regulates the cell cycle. Because
netrin
is so influential in the regulation of cell death, the gene coding for
netrin
("NTN1") is considered to be an oncogene.
Netrin
-1 has also been shown to act as a chemorepellent "in vivo" for trochlear motor axons that migrate dorsally away from the floor plate. Interestingly, in
Netrin
-1 deficient mice, trochlear axon projections are normal, suggesting the existence of other redundant guidance cues working in tandem with
Netrin
-1 to repel trochlear axons.
When it was understood that DCC apoptosis may also be overcome by
netrin
-1 overexpression, colorectal cancers were assessed for
netrin
-1 overexpression, and a small but significant percent of these cancers were found to vastly overexpress the molecule.
Netrin
-1 is a protein that in humans is encoded by the "NTN1" gene.
Netrin
-G2 is a protein that in humans is encoded by the "NTNG2" gene.
Netrin
receptor UNC5A is a protein that in humans is encoded by the "UNC5A" gene.
Netrin
-G1 is a protein that in humans is encoded by the "NTNG1" gene.
A study was performed to determine the effect of
netrin
-1 on schwann cell proliferation. Unc5b is the sole receptor expressed in RT4 schwannoma cells and adult primary Schwann cells, and
netrin
-1 and Unc5b are found to be expressed in the injured sciatic nerve. It was also found that the
netrin
-1-induced Schwann cell proliferation was blocked by the specific inhibition of Unc5b expression with RNAi. These data suggests that
netrin
-1 could be an endogenous trophic factor for Schwann cells in the injured peripheral nerves.
DCC can be considered a conditional tumour suppressor gene as well as a conditional oncogene. When DCC is present and not activated by
netrin
it is proapoptotic, and represses tumour formation. When DCC is present and
netrin
-activated it promotes cell survival, acting as an oncoprotein.
Netrin
-activated DCC is known to activate the CDC42-RAC1 and MAPK1/3 pathways, both of which are activated in cancer and promote tumour development.
The first coding exon contains the whole of the frizzled-related cysteine rich domain (CRD), while the third exon (COOH-terminal domain) contains the
netrin
-related domain.
Netrin
is a regulator of apoptosis; the SFRP1
netrin
-related motif is also found in a range of other proteins that is thought to mediate protein-protein interactions. The middle exon most likely represents a spacer between the first and third exon. There are 2 introns present within the coding sequence of SFRP1.