Neuropilin is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

receptor Receptor may refer to: * Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...

active in

neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...

s. There are two forms of Neuropilins,

NRP-1 Neuropilin-1 is a protein that in humans is encoded by the ''NRP1'' gene. In humans, the neuropilin 1 gene is located at 10p11.22. This is one of two human neuropilins. Function NRP1 is a membrane-bound coreceptor to a tyrosine kinase recepto ...

and NRP-2. Neuropilins are transmembrane

glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...

s, first documented to regulate

neurogenesis Neurogenesis is the process by which nervous system cells, the neurons, are produced by neural stem cells (NSCs). It occurs in all species of animals except the porifera (sponges) and placozoans. Types of NSCs include neuroepithelial cells (NECs) ...

and

angiogenesis Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature by processes of sprouting and splitting ...

by complexing with Plexin receptors/class-3

semaphorin Semaphorins are a class of secreted and membrane proteins that were originally identified as axonal growth cone guidance molecules. They primarily act as short-range inhibitory signals and signal through multimeric receptor complexes. Semaphorins ...

ligands and Vascular Endothelial Growth Factor (VEGF) receptors/VEGF ligands, respectively. Neuropilins predominantly act as co-receptors as they have a very small

cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...

ic domain and thus rely upon other cell surface receptors to transduce their signals across a

cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...

. Recent studies have shown that Neuropilins are multifunctional and can partner with a wide variety of transmembrane receptors. Neuropilins are therefore associated with numerous signalling pathways including those activated by

Epidermal Growth Factor Epidermal growth factor (EGF) is a protein that stimulates cell growth and differentiation by binding to its receptor, EGFR. Human EGF is 6-k Da and has 53 amino acid residues and three intramolecular disulfide bonds. EGF was originally descr ...

(EGF), Fibroblast Growth Factor (FGF), Hepatocyte Growth Factor (HGF), Insulin-like Growth Factor (IGF), Platelet Derived Growth Factor (PDGF) and

Transforming Growth Factor beta Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other sign ...

(TGFβ). Although Neuropilins are commonly found at the cell surface, they have also been reported within the mitochondria and nucleus. Both Neuropilin family members can also be found in soluble forms created by

alternative splicing Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be ...

or by ectodomain shedding from the cell surface. The pleiotropic nature of the NRP receptors results in their involvement in cellular processes, such as

axon guidance Axon guidance (also called axon pathfinding) is a subfield of neural development concerning the process by which neurons send out axons to reach their correct targets. Axons often follow very precise paths in the nervous system, and how they mana ...

and

, the

immune response An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...

and remyelination. Therefore, dysregulation of NRP activity has been implicated in many pathological conditions, including many types of

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

and

cardiovascular disease Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, h ...

Applications

Neuropilin-1 is a therapeutic target protein in the treatment for

leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...

and

lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlar ...

, since It has been shown that there is increased expression in neuropilin-1 in leukemia and lymphoma cell lines. Also, antagonism of neuropilin-1 has been found to inhibit tumour

cell migration Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing and immune responses all require the orchestrated movement of cells in particular dire ...

and

adhesion Adhesion is the tendency of dissimilar particles or surfaces to cling to one another ( cohesion refers to the tendency of similar or identical particles/surfaces to cling to one another). The forces that cause adhesion and cohesion can be ...

Structure

Neuropilins contain the following four domains: *

N-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...

CUB domain (for complement C1r/C1s, Uegf, Bmp1) * Coagulation factor 5/8 type, C-terminal (

discoidin domain Discoidin domain (also known as F5/8 type C domain, or C2-like domain) is major protein domain of many blood coagulation factors. Blood coagulation factors V and VIII contain a C-terminal, twice repeated, domain of about 150 amino acids, whic ...

) *

MAM domain MAM domain is an evolutionary conserved protein domain. It is an extracellular domain found in many receptors. A 170 amino acid domain, the so-called MAM (meprin, A-5 protein, and receptor protein-tyrosine phosphatase mu) domain, has been recog ...

(for meprin, A-5 protein, and receptor protein-tyrosine phosphatase mu) * C-terminal neuropilin The structure of B1 domain (coagulation factor 5/8 type) of neuropilin-1 was determined through X-Ray Diffraction with a resolution of 2.90 Å. The secondary structure of this domain is 5% alpha helical and 46%

beta sheet The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a g ...

. Ramachandran plot.

References

External links

* {{Transmembrane receptors Transmembrane receptors Single-pass transmembrane proteins