Disease relevance of Nrtn

• Analysis of capsaicin-evoked Ca2+ transients in dissociated mouse dorsal root ganglion (DRG) neurons revealed that a 7 min exposure to GDNF, neurturin, or artemin potentiated TRPV1 function at doses 10-100 times lower than NGF [1].
• Here, we report the ability of glial cell line-derived neurotrophic factor (GDNF) family members artemin, neurturin and GDNF to potentiate TRPV1 signaling and to induce behavioral hyperalgesia [1].
• Neurturin-deficient mice develop dry eye and keratoconjunctivitis sicca [2].

High impact information on Nrtn

• Neurturin responsiveness requires a GPI-linked receptor and the Ret receptor tyrosine kinase [3].
• Subsets of parasympathetic and enteric neurons require neurturin signaling via glial cell line-derived neurotrophic factor family receptor alpha2 (GFRalpha2) for development and target innervation [4].
• Retarded growth and deficits in the enteric and parasympathetic nervous system in mice lacking GFR alpha2, a functional neurturin receptor [5].
• Parasympathetic innervation of the lacrimal and submandibular salivary gland is dramatically reduced in NTN-/- mice, indicating that Neurturin is a neurotrophic factor for parasympathetic neurons [6].
• Neurturin-deficient (NTN-/-) mice generated by homologous recombination are viable and fertile but have defects in the enteric nervous system, including reduced myenteric plexus innervation density and reduced gastrointestinal motility [6].

Biological context of Nrtn

• Seizure activity regulates gene expression for glial cell line-derived neurotrophic factor (GDNF) and neurturin (NRTN), and their receptor components, the transmembrane c-Ret tyrosine kinase and the glycosylphosphatidylinositol-anchored GDNF family receptor (GFR) alpha 1 and alpha 2 in limbic structures [7].
• Both GDNF and neurturin induced neural crest cell migration and neurite outgrowth in all regions examined [8].
• These two forms do not share high sequence homologies with the recently isolated neurturin receptor [9].
• Transient disruption of spermatogenesis by deregulated expression of neurturin in testis [10].
• Neurturin, a novel neurotrophic factor, is localized to mouse chromosome 17 and human chromosome 19p13.3 [11].

Anatomical context of Nrtn

• Neurturin is expressed in postnatal cerebral cortex, striatum, several brainstem areas, and the pineal gland [12].
• Applied locally on agarose beads, neurturin induces supernumerary ureteric buds to emerge from the wolffian duct and causes nearby collecting duct branches to distend to an abnormally large diameter [13].
• Glial-cell-line-derived neurotrophic factor (GDNF) and neurturin (NTN) are structurally related to TGF-beta and are survival factors for sympathetic, sensory, and central nervous system neurons [14].
• We have studied expression and function of GDNF, neurturin, GFRalpha-1, and GFRalpha-2 in murine skin during the cyclic transformation of the hair follicle (HF) from its resting state (telogen) to active growth (anagen) and then through regression (catagen) back to telogen [15].
• PURPOSE: Neurturin (NTN) and its receptor components (GFRalpha2 and Ret) play an important role in the survival of different populations of neurons in the central and peripheral nervous systems [16].

Associations of Nrtn with chemical compounds

• Our findings indicate that GDNF and neurturin promote neuronal survival by signalling through similar multicomponent receptors that consist of a common receptor tyrosine kinase and a member of a GPI-linked family of receptors that determines ligand specificity [3].
• Loss of nitrergic neurotransmission to mouse corpus cavernosum in the absence of neurturin is accompanied by increased response to acetylcholine [17].
• However, we report here that GDNF and neurturin blocked the growth inhibitory and neuritogenic effects of all-trans-retinoic acid in neuroblastoma cells in vitro [18].

Physical interactions of Nrtn

• The glial cell line-derived neurotrophic factor (GDNF) family receptor GFRalpha2 is the binding receptor for neurturin (NRTN) [19].

Regulatory relationships of Nrtn

• We conclude that GDNF and neurturin potently upregulate functional B1 receptor expression in small non-peptidergic nociceptive neurones [20].

Other interactions of Nrtn

• These analyses demonstrate that glial cell line-derived neurotrophic factor (GDNF) and neurturin are important for different aspects of ENS development [21].
• Neurturin and GDNFR-beta were present in developing sensory organs [12].
• Neurturin (NRTN), signalling via the GDNF family receptor alpha2 (GFRalpha2) and Ret tyrosine kinase, has recently been identified as an essential target-derived factor for many parasympathetic neurons [22].
• Neurturin (NRTN) is a neurotrophic factor required during development for normal cholinergic innervation of the heart, but whether NRTN continues to function in the adult heart is unknown [23].
• It seems likely that the GDNF-independent population represent MNs that require other GDNF family members (neurturin, persephin, artemin) for their survival [24].

Analytical, diagnostic and therapeutic context of Nrtn

• Gene targeting reveals a critical role for neurturin in the development and maintenance of enteric, sensory, and parasympathetic neurons [6].
• We have used interspecific backcross analysis to localize neurturin to mouse chromosome 17 near the Vav locus and fluorescence in situ hybridization analysis to localize human neurturin to the syntenic region of human chromosome 19p13.3 [11].

References