netrin - Synonyms for netrin | Synonyms Of netrin

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.