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M J Radeke

Publications and source records attributed to M J Radeke.

23 records · Page 2Linked to original sources
PubMed1988

Developmental and regional expression of beta-nerve growth factor receptor mRNA in the chick and rat.

Hybridization probes from the transmembrane region of the chick NGF receptor (NGF-R) that show high homology with the rat NGF-R were used to demonstrate an abundant 4.5 kb NGF-R mRNA in the chick embryo at E3.5. The level remained high until E12 but decreased to adult levels by E18. The highest levels at E8 were in spinal cord, bursa of Fabricius, gizzard, femoralis muscle, and skin. In situ hybridization to E7 embryos showed high expression of the NGF-R gene in spinal cord, particularly the lateral motor column, and in dorsal root, sympathetic, and nodose ganglia. NGF-R mRNA expression was observed throughout brain development and in all regions of the adult brain, with high levels in cerebellum and septum. Lymphoid tissues of chick and rat also expressed the receptor. The complex and widespread expression of NGF-R mRNA in areas not known to be NGF targets suggests broader functions for NGF.

Amino Acid Sequence↗
PubMed1987

Differential regulation of mRNA encoding nerve growth factor and its receptor in rat sciatic nerve during development, degeneration, and regeneration: role of macrophages.

In newborn rats the levels of nerve growth factor (NGF) mRNA (mRNANGF) and NGF receptor mRNA (mRNA(rec)) in the sciatic nerve were 10 and 120 times higher, respectively, than in adult animals. mRNA(rec) levels decreased steadily from birth, approaching adult levels by the third postnatal week, whereas mRNANGF levels decreased only after the first postnatal week, although also reaching adult levels by the third week. Transection of the adult sciatic nerve resulted in a marked biphasic increase in mRNANGF with time. On the proximal side of the cut, this increase was confined to the area immediately adjacent to the cut; peripherally, a similar biphasic increase was present in all segments. mRNA(rec) levels were also markedly elevated distal to the transection site, in agreement with previous results obtained by immunological methods [Taniuchi, M., Clark, H. B. & Johnson, E. M., Jr. (1986) Proc. Natl. Acad. Sci. USA 83, 4094-4098]. Following a crush lesion (allowing regeneration), the mRNA(rec) levels were rapidly down-regulated as the regenerating nerve fibers passed through the distal segments. Down-regulation of mRNANGF also occurred during regeneration but was slower and not as extensive as that of mRNA(rec) over the time period studied. Changes in mRNANGF and mRNA(rec) occurring in vivo after transection were compared with those observed in pieces of sciatic nerve kept in culture. No difference was found for mRNA(rec). Only the initial rapid increase in mRNANGF occurred in culture, but the in vivo situation could be mimicked by the addition of activated macrophages. This reflects the situation in vivo where, after nerve lesion, macrophages infiltrate the area of the Wallerian degeneration. These results suggest that mRNANGF synthesis in sciatic non-neuronal cells is regulated by macrophages, whereas mRNA(rec) synthesis is determined by axonal contact.

Animals↗
PubMed1987

Nerve growth factor in neuronal development and maintenance.

One of the major roles of nerve growth factor (NGF) is to mediate the selective survival of a proportion of the developing sympathetic and sensory neurones as they innervate their particular target tissues. The underlying basis of this phenomenon is the synthesis of limited amounts of NGF in the target, its secretion around, and uptake by, the nerve terminal and its retrograde transport along axons to the neuronal cell bodies. The cascades of reactions which lead to neuronal survival and maintenance are initiated by signal transduction somewhere in this pathway. Retrograde transport and the initial signal transduction step begin when NGF binds to NGF receptors on the nerve terminal. Receptor-mediated internalization and the survival and maintenance function of NGF are mediated by the higher affinity receptors. These receptors have relative molecular masses of approx. 145,000 and are trypsin-resistant when occupied. In contrast, the larger population of lower affinity receptors have relative molecular masses of 85,000 and are rapidly degraded by trypsin. Clustering of the lower affinity receptors by a variety of agents gives them many of the characteristics of the higher affinity receptors, suggesting receptor interconversion may play a role in NGF actions. The structure of the lower affinity NGF receptor, determined by gene transfer and cloning, shows it to be a unique, heavily glycosylated protein. The extracellular domain is rich in cysteine-containing repeat units while the intracellular domain lacks the consensus sequence for an endogenous kinase activity. It is likely that the higher affinity receptor contains this protein as the NGF binding subunit together with a second protein which determines both the nature of the signal transduction mechanism and the process of internalization.

Animals↗
PubMed1986

cGMP influences guanine nucleotide binding to frog photoreceptor G-protein.

A rapid light-induced decrease in cGMP is thought to play a role in regulating the permeability or light sensitivity of photoreceptor membranes. Photo-excited rhodopsin activates a guanine nucleotide-binding protein (G-protein) by catalyzing the exchange of bound GDP for GTP. This G-protein X GTP complex activates the phosphodiesterase resulting in a decrease in cGMP concentration. We have observed two processes in vitro which may be relevant for the regulation of G-protein activation. First, we have found that free GDP binds to G-protein with an affinity similar to that of GTP. These two nucleotides appear to compete for a common site. Since G-protein X GDP does not activate phosphodiesterase, light-induced changes in the GTP/GDP ratio known to occur on illumination may serve to reduce G-protein activation and hence reduce phosphodiesterase activation. Second, addition of cGMP in the presence of equimolar GTP and GDP causes GTP binding to G-protein to be enhanced compared to GDP binding. This effect increases as the cGMP concentration is increased from 0.05 to 2 mM. Thus, light-induced decreases in cGMP concentration may also act as a feedback control in reducing G-protein activation. One or both of these processes may be involved in the desensitization (light adaptation) of rod photoreceptors.

Animals↗