title: ProNGF promotes neurite growth from a subset of NGF-dependent neurons by a p75NTR-dependent mechanism.
abstract: The somatosensory and sympathetic innervation of the vertebrate head is derived principally from the neurons of trigeminal and superior cervical ganglia (SCG), respectively. During development, the survival of both populations of neurons and the terminal growth and branching of their axons in the tissues they innervate is regulated by the supply of nerve growth factor (NGF) produced by these tissues. NGF is derived by proteolytic cleavage of a large precursor protein, proNGF, which is recognised to possess distinctive biological functions. Here, we show that proNGF promotes profuse neurite growth and branching from cultured postnatal mouse SCG neurons. In marked contrast, proNGF does not promote the growth of trigeminal neurites. Studies using compartment cultures demonstrated that proNGF acts locally on SCG neurites to promote growth. The neurite growth-promoting effect of proNGF is not observed in SCG neurons cultured from p75(NTR)-deficient mice, and proNGF does not phosphorylate the NGF receptor tyrosine kinase TrkA. These findings suggest that proNGF selectively promotes the growth of neurites from a subset of NGF-responsive neurons by a p75(NTR)-dependent mechanism during postnatal development when the axons of these neurons are ramifying within their targets in vivo.
authors: Molecular Biosciences Division, School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AT, Wales, UK. HowardLJ@cf.ac.uk
authors: Laura
authors: L
authors: Howard
authors: Sean
authors: S
authors: Wyatt
authors: Guhan
authors: G
authors: Nagappan
authors: Alun M
authors: AM
authors: Davies
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D020932:Nerve Growth Factor / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism; D016501:Neurites / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D020917:Receptor, trkA / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014276:Trigeminal Nerve / Q000378:metabolism
chemical_list: D009414:Nerve Growth Factors; D034741:RNA, Small Interfering; D017475:Receptors, Nerve Growth Factor; C517634:Ngfr protein, mouse; D020932:Nerve Growth Factor; D020917:Receptor, trkA
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