mNGF 7S
Mouse Nerve Growth Factor 7S
Mouse submaxillary glands
The neurotrophins ("neuro" means nerve and "trophe" means nutrient) are a family of soluble, basic growth factors which regulate neuronal development, maintenance, survival and death in the CNS and the PNS. NGF, the first member of the family to be discovered, was originally purified as a factor able to support survival of sympathetic and sensory spinal neurons in culture. It is synthesized and secreted by sympathetic and sensory target organs and provides trophic support to neurons as they reach their final target. Neurotrophin secretion increases in the nervous system following injury. Schwann cells, fibroblasts, and activated mast cells normally synthesize NGF constitutively; however direct trauma and induction of cytokines combine to increase neurotrophin production in these cells after injury.
NGF is purified in three forms: the 7S, 2.5S and beta. The 7S, 130 kDa, form occurs naturally in mouse submaxillary glands, and is a multimeric protein composed of two alpha, one beta and two gamma subunits. The name is derived from its sedimentation co-efficient, 7S. The biologically active subunit is the beta, which is a 26 kDa dimer composed of two identical 120 amino acid chains held together by hydrophobic interactions. The alpha chain stabilizes the 7S complex and binds two zinc ions per 7S complex as cofactor at the beta-gamma interface. The gamma chain is an arginine specific protease; it may also have plasminongen activator activity as well as mitogenic activity for chick embryo fibroblasts. The 2.5S form is 9 amino acids shorter than the beta form, because of proteolysis that occurs during the purification process.
The structural hallmark of all the neurotrophins is the characteristic arrangement of the disulfide bridges known as the cysteine knot, which has been found in other growth factors such as Platelet-Derived Growth Factor. There is a 95.8% homology between the rat and mouse forms, and an 85% homology between the human and mouse.
NGF has been shown to regulate neuronal survival, development function and plasticity. Recently, involvement of NGF in processes not involving neuronal cells has been shown, such as asthma, psoriasis and wound healing. The biological effects of NGF are mediated by two receptors: TrkA, which is specific for NGF and p75, which binds all the neurotrophins.
Neurotrophic Factors, Nerve Growth Factors, NGF