Glial Fibrillary Acidic Protein (GFAP) is an intermediate filament (IF) protein which belongs to the intermediate filament family. GFAP is expressed in numerous cell types of the central nervous system (CNS), ependymal cells and phosphorylated by PKN1. GFAP, a class-III intermediate filament, is a cell-specific marker during the development of the central nervous system and distinguishes astrocytes from other glial cells. It is closely related to its non-epithelial family members, vimentin, desmin, and peripherin, which are all involved in the structure and function of the cell’s cytoskeleton. GFAP is thought to help to maintain astrocyte mechanical strength, as well as the shape of cells but its exact function remains poorly understood.
GFER is a hepatotrophic growth factor and flavin-linked sulfhydryl oxidase which belongs to the Erv1/ALR family of proteins. GFER is widely expressed in various human tissues. They are two isoforms of this protein. Isoform 1 could regenerate the redox-active disulfide bonds in CHCHD4/MIA40, a chaperone essential for disulfide bond formation and protein folding in the mitochondrial intermembrane space. The reduced form of CHCHD4/MIA40 forms a transient intermolecular disulfide bridge with GFER/ERV1, resulting in regeneration of the essential disulfide bonds in CHCHD4/MIA40, while GFER/ERV1 becomes re-oxidized by donating electrons to cytochrome c or molecular oxygen. Isoform 2 may act as an autocrine hepatotrophic growth factor promoting liver regeneration. GFER could also induce the expression of S-adenosylmethionine decarboxyl-ase and ornithine decarboxylases (ODC). S-adenosylmethionine decarboxyl-ase and ornithine decarboxylases play an important role in the synthesis of polyamines.
Glial cell line derived neurotrophic factor (GDNF) Family Receptor Alpha 1 (GFRA1) is a member of the GDNF receptor family. It is a glycosylphosphatidylinositol (GPI)-linked cell surface receptor for both GDNF and NTN, and mediates activation of the RET tyrosine kinase receptor. GFRA1 is a potent survival factor for central and peripheral neurons, and is essential for the development of kidneys and the enteric nervous system. Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) are its binding ligand which are two structurally related, potent neurotrophic factors that play key roles in the control of neuron survival and differentiation. GDNF promotes the formation of a physical complex between GFRA/GDNFRa and the orphan tyrosin kinase receptor Ret, thereby inducing its tyrosine phosphorylation. The RET is a receptor tyrosine kinase representing the signal-transducing molecule of a multisubunit surface receptor complex for the GDNF, in which GFRA / GDNFRa acts as the ligand-binding component. GDNF, a distantly related member of the transforming growth factor-β (TGF-â) superfamily, and its receptor components: GFRA1, Ret and neural cell adhesion molecule (NCAM) have been recently reported to be expressed in the testis and to be involved in the proliferation regulation of immature Sertoli cells.
Glial Cell Line-Derived Neurotrophic Factor Family Receptor α-1 (GDNFRα1) is a glycosylphosphatidylinositol (GPI) linked cell surface protein belonging to GDNF-family receptor α subtype which consists of at least four members. GFRα1and GFRα2 are the cognate co-receptor for the neurotrophic factor neurturin mediating the NRTN-induced autophosphorylation and activation of the RET tyrosine kinase receptor. Soluble GFRαs released enzymatically from the cell surface by phosphatidylinositol phospholipase C, as well as recombinantly produced soluble GFRα1, can also bind with high affinity to GDNF and trigger the activation of Ret tyrosine kinase. Human GFRα1 shares 93% amino acid identity with mouse GFRα1.The expression of the various GFRαs are differentially regulated in the central and peripheral nervous system, suggesting complementary roles for the GFRαs in mediating the activities of the GDNF family of neurotrophic factors.
Glial cell line derived neurotrophic factor (GDNF) Family Receptor Alpha 3 (GFRA3) or GDNFRa3 is a member of the GDNF receptor family. It is a glycosylphosphatidylinositol (GPI)-linked cell surface receptor for both GDNF and NTN, and mediates activation of the RET tyrosine kinase receptor. GFRA3 / GDNFRa3 is a potent survival factor for central and peripheral neurons, and is essential for the development of kidneys and the enteric nervous system. Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) are its binding ligand which are two structurally related, potent neurotrophic factors that play key roles in the control of neuron survival and differentiation. GDNF promotes the formation of a physical complex between GFRA/GDNFRa and the orphan tyrosin kinase receptor Ret, thereby inducing its tyrosine phosphorylation. The RET is a receptor tyrosine kinase representing the signal-transducing molecule of a multisubunit surface receptor complex for the GDNF, in which GFRA / GDNFRa acts as the ligand-binding component. The neurotrophic growth factor artemin binds selectively to GDNF family receptor α3 (GFRA3 / GDNFRa3), forming a molecular complex with the co-receptor RET which mediates downstream signaling. This signaling pathway has been demonstrated to play an important role in the survival and maintenance of nociceptive sensory neurons and in the development of sympathetic neurons.
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