Neurturin and Glial Cell Line-Derived Neurotrophic Factor Receptor-β (GDNFR-β), Novel Proteins Related to GDNF and GDNFR-α with Specific Cellular Patterns of Expression Suggesting Roles in the Developing and Adult Nervous System and in Peripheral Organs

Abstract

Cloning strategies were used to identify a gene termed glial cell line-derived neurotrophic factor receptor-␤ (GDNFR-␤) related to GDNFR-␣. In situ hybridization was then used to map cellular expression of the GDNF-related trophic factor neurturin (NTN) and GDNFR-␤ mRNA in developing and adult mice, and comparisons with GDNFR-␣ and RET were made. Neurturin is expressed in postnatal cerebral cortex, striatum, several brainstem areas, and the pineal gland. GDNFR-␤ mRNA was more widely expressed in the developing and adult CNS, including cerebral cortex, cerebellum, thalamus, zona incerta, hypothalamus, brainstem, and spinal cord, and in subpopulations of sensory neurons and developing peripheral nerves. NTN colocalized with RET and GDNFR-␣ in ureteric buds of the developing kidney. The circular muscle layer of the developing intestines, smooth muscle of the urether, and developing bronchiolae also expressed NTN. GDNFR-␤ was found in myenteric but not submucosal intestinal plexuses. In developing salivary glands NTN had an epithelial expression, whereas GDNFR-␤ was expressed in surrounding tissue. Neurturin and GDNFR-␤ were present in developing sensory organs. In the gonads, NTN appeared to be expressed in Sertoli cells and in the epithelium of the oviduct, whereas GDNFR-␤ was expressed by the germ cell line. Our findings suggest multiple roles for NTN and GDNFR-␤ in the developing and adult organism. Although NTN and GDNFR-␤ expression patterns are sometimes complementary, this is not always the case, suggesting multiple modi operandi of GDNF and NTN in relation to RET and the two binding proteins, GDNFR-␣ and GDNFR-␤.

Neurturin Influences Inflammatory Responses and Airway Remodeling in Different Mouse Asthma Models

“…Previous reports have shown the expression of NTN, RET, and GFRa-2 in the airways (17,18,29). Our results demonstrated the mRNA expression of GFRa-2 and RET in the LA-4 cell line, WT BMDCs, and spleen DCs.…”

“…In addition to this interaction, NTN might cross-talk weakly with the receptor GFRa-1 (16). Expression of NTN, RET, and GFRa-2 mRNAs was observed during the development of the respiratory system (17). In adult mice, NTN was detected at a moderate level in the lung alveoli and in the thymus (18).…”

Regulation of the Development of Mesencephalic Dopaminergic Systems by the Selective Expression of Glial Cell Line-Derived Neurotrophic Factor in Their Targets

“…GDNF mRNA is highly expressed in the striatum during development (Schaar et al, 1993;Stromberg et al, 1993;Blum and Weickert, 1995;Choi-Lundberg and Bohn, 1995;Golden et al, 1999), and we have shown by quantitative analysis that its highest level of expression is on PND 2 (Cho et al, 2003), during the first phase. The receptor for GDNF, GDNF receptor ␣1 (GFR␣1), and its signaling tyrosine kinase, Ret, are both highly expressed in SNpc during development (Widenfalk et al, 1997;Yu et al, 1998). As expected for a target-derived factor, GDNF can be specifically transported retrograde from striatum to SNpc (Tomac et al, 1995b).…”

Full activation of MEN2B mutant RET by an additional MEN2A mutation or by ligand GDNF stimulation

“…This would depend on the availability of Ret ligands and accessory proteins in the tissues aected in MEN2B. Unfortunately, even though dierent studies have been reported on the expression of Ret ligands and of the relative coreceptors (Trupp et al, 1997;Widenfalk et al, 1997), there are no data concerning MEN2B aected tissue and the derived tumours. It has been reported that GDNF stimulation of Ret autophosphorylation and activity is dependent on one of two cell-surface-associated accessory proteins, designated GDNFRa (Jing et al, 1996;Treanor et al, 1996) and GDNFRb (Suvanto et al, 1997;Baloh et al, 1997;Sanicola et al, 1997).…”