Sandbox Reserved 1658: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<p align="justify">Neuropilin-1 has three different domains<ref name="structural study"/>. A cytoplasmic domain which contains 40 residues, a transmembrane domain which contains 24 residues and a 850-residues ectodomain<ref name="human neuropilin">Christian C. Lee, Andreas Kreusch,Daniel McMullan, Ken Ng, and Glen Spraggon Crystal Structure of the HumanNeuropilin-1 b1 Domain https://www.cell.com/structure/pdf/S0969-2126(02)00941-3.pdf</ref>. The latter is an assembly of five individual motifs (a1,<scene name='86/868191/A2_domain/1'>a2</scene>,<scene name='86/868191/B1_domain/1'>b1</scene>,<scene name='86/868191/B2_domain/1'>b2</scene> and c). It contains, hence two [https://en.wikipedia.org/wiki/CUB_domain CUB domains] (a1/a2), two homologous domains to coagulation factors V/VIII (b1/b2) and a [https://en.wikipedia.org/wiki/MAM_domain MAM domain] (c). The ligand binding is mediated by the (a1/a2) and (b1/b2) portion of the ectodomain while the c domain mediates | <p align="justify">Neuropilin-1 has three different domains<ref name="structural study"/>. A cytoplasmic domain which contains 40 residues, a transmembrane domain which contains 24 residues and a 850-residues ectodomain<ref name="human neuropilin">Christian C. Lee, Andreas Kreusch,Daniel McMullan, Ken Ng, and Glen Spraggon Crystal Structure of the HumanNeuropilin-1 b1 Domain https://www.cell.com/structure/pdf/S0969-2126(02)00941-3.pdf</ref>. The latter is an assembly of five individual motifs (a1,<scene name='86/868191/A2_domain/1'>a2</scene>,<scene name='86/868191/B1_domain/1'>b1</scene>,<scene name='86/868191/B2_domain/1'>b2</scene> and c). It contains, hence two [https://en.wikipedia.org/wiki/CUB_domain CUB domains] (a1/a2), two homologous domains to coagulation factors V/VIII (b1/b2) and a [https://en.wikipedia.org/wiki/MAM_domain MAM domain] (c). The ligand binding is mediated by the (a1/a2) and (b1/b2) portion of the ectodomain while the c domain mediates Neuropilin oligomerization. However MAM domain isn't able to support on its own multimerization of NRP molecules. So, it might contribute to the assembly and regulation of the signaling complexes by positionning the other extracellular domains of NRPs away from the membrane.<ref name="MAM domain">PMID: 27720589</ref></p> | ||
<p align="justify"> For example, the semaphorins (SEMA) bind to the (a1/a2/b1) domains while Vascular endothelial growth factors (VEGFs) bind to (b1/b2)<ref name="structural study"/>. The c domain as well as the transmembrane domain, is involved in the receptor dimerization. The cytoplasmic domain does not contain a binding domain but a [https://en.wikipedia.org/wiki/PDZ_domain PDZ domain]. This segment is only 42-44 amino acids length and by the way hasn't any catalytic function. It participates in the formation and stimulation of signalling complexes.</p> | <p align="justify"> For example, the semaphorins (SEMA) bind to the (a1/a2/b1) domains while Vascular endothelial growth factors (VEGFs) bind to (b1/b2)<ref name="structural study"/>. The c domain as well as the transmembrane domain, is involved in the receptor dimerization. The cytoplasmic domain does not contain a binding domain but a [https://en.wikipedia.org/wiki/PDZ_domain PDZ domain]. This segment is only 42-44 amino acids length and by the way hasn't any catalytic function. It participates in the formation and stimulation of signalling complexes.</p> | ||
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<p align="justify">In mature organisms, neuropilins primarily perform the role of pro-angiogenic co-receptors<ref name="cardiovascular development">PMID: 26451046</ref>. Neuropilin-1 works as a specific co-receptor of VEGFR-2 for VEGF-A. After binding and activation, neuropilins promote angiogenesis by stabilizing the VEGF/VEGFR<ref name="cardiovascular development"/> binding. | <p align="justify">In mature organisms, neuropilins primarily perform the role of pro-angiogenic co-receptors<ref name="cardiovascular development">PMID: 26451046</ref>. Neuropilin-1 works as a specific co-receptor of VEGFR-2 for VEGF-A. After binding and activation, neuropilins promote angiogenesis by stabilizing the VEGF/VEGFR<ref name="cardiovascular development"/> binding. | ||
Researchers also think that neuropilins affect the vascular motility of endothelial cells, independently of their action on the protein complex VEGF/VEGFR. Besides, NRP1 enhances the signalling of the extra-cellular matrix in endothelial cells. | Researchers also think that neuropilins affect the vascular motility of endothelial cells, independently of their action on the protein complex VEGF/VEGFR. Besides, NRP1 enhances the signalling of the [https://en.wikipedia.org/wiki/Extracellular_matrix extra-cellular matrix] in endothelial cells. | ||
</p> | </p> | ||
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<h5>In the immune system</h5> | <h5>In the immune system</h5> | ||
<p align="justify">An expression of NRP1 has been detected in several cells of the immune system such as macrophages, dendritic cells, but also in T cell subsets. In dendritic cells and T cells subsets, NRP1 helps to trigger the immune response. Researchers also think that NRP1 could represent à new activation marker for T cells.</p> | <p align="justify">An expression of NRP1 has been detected in several cells of the immune system<ref name="immunity>DOI 10.3389/fimmu.2017.01228</ref> such as macrophages, dendritic cells, but also in T cell subsets. In dendritic cells and T cells subsets, NRP1 helps to trigger the immune response. Researchers also think that NRP1 could represent à new activation marker for T cells.</p> | ||
== Disease == | == Disease == | ||
