About NRP / Neuropilin:
Neuropilin is a protein reception which is active in neurons, and was first discovered in the optic tectum of Xenopus laevis before later being found in the developing brain. Neuropilins are separated into two categories, known as NRP-1 and NRP-2. They are what’s known as ‘transmembrane glycoproteins’ and serve the predominant function of being co-receptors for semaphorins, which are another, similar, form of proteins. They are specific receptors for class-3 semaphorins, as well as several other members of the vascular endothelial growth factor (VEGF) family, which serve the function of being the main regulator of blood and lymphatic vessel growth - an essential within the human body.
Focusing on how Neuropilin helps class-3 semaphorins, we must first understand their function. Class-3 semaphorins have many responsibilities, but primarily they handle axon guidance during the development of the nervous system, more specifically, in vertebrates. The reason that Neuropilins are so good as co-receptors for the semaphorins is due to their pleiotropic nature; which means they influence two or more seemingly unrelated phenotypic traits. This means if and when they mutate, they can affect several traits at once as they have the same signalling function. Neuropilins help here as they are involved in these multiple signalling pathways, including but not limited to axon guidance, immune response, remyelination and angiogenesis.
A specific understanding however of Neuropilin-1 has not been possible, due to the different ways that this manifests between mice and humans; for example, in mice it manifests as selective expressions on thymic-derived Tregs, and is greatly influential in increasing immunosuppressive function. However, in humans this manifestation is not seen, and instead, Neuropilin-1 expresses itself in plasmacytoid dendritic cells, and is primarily responsible for priming immune responses. The full mechanism by which this activity is mediated, and why these differences manifest between species is unclear and therefore should continue to be studied for years to come.
Neuropilins have an extremely small cytoplasmic domain, and therefore rely on other molecules (usually Plexins, which are other proteins, also acting as receptors for Semaphorin) to send their signals across a cell membrane. They are commonly found working as dimers (which are complexes formed by two protein monomers, non-covalently bound), and produce different combinations and solutions for different molecules.
Studies have shown promising results in applying Neuropilin-1 as a target protein for therapeutic use in the treatment of lymphomas and leukemias; due to its increased expression in leukemia and lymphoma cell lines. It has also been shown to inhibit the growth, adhesion and migration of tumours when antagonised.
There are four domains which make up a Neuropilin, which are as follows:
● C-terminal Neuropilin
● N-terminal CUB domain
● Coagulation factor 5/8 type C-terminal
● MAM domain
B1’s domain and structure of Neuropilin-1 were discovered and documented through an X-ray diffraction method using a 2.90 resolution. This was also found to have a secondary structure of 46% beta sheet and 5% alpha helical.