Association of 125I-nerve growth factor with PC12 pheochromocytoma cells. Evidence for internalization via high-affinity receptors only and for long-term regulation by nerve growth factor of both high- and low-affinity receptors.

Bernd, Paulette; Greene, LA

doi:10.1016/s0021-9258(17)42578-6

Cited by 188 publications

(34 citation statements)

References 49 publications

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“…Several other possible modes of action of Li + can apparently be ruled out. As assessed by methods described elsewhere (40), LiC1 at concentrations up to 20 mM had no effect on the capacity of PCI2 cells to bind or internalize ~251-NGF. Also, the effect of Li + did not appear to be due to general suppression of protein synthesis since incorporation of [35S]methionine into trichloroacetic acid (TCA)-precipitable counts by PCl2 cells over 2 h was unaffected by 5-10 mM LiCI.…”

Section: Possible Mechanisms O[ the Inhibitory Action Of LI +mentioning

confidence: 99%

Lithium ion inhibits nerve growth factor-induced neurite outgrowth and phosphorylation of nerve growth factor-modulated microtubule-associated proteins.

Burstein¹,

Seeley²,

Greene³

1985

The Journal of Cell Biology

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LiCI (2.5-20 mM) reversibly suppressed nerve growth factor (NGF)-induced neurite outgrowth by cultured rat PC12 pheochromocytoma cells. Similar concentrations of LiCI also reversibly blocked NGF-dependent regeneration of neurites by PC12 cells that had been primed by long-term pre-exposure to NGF and by cultured newborn mouse sympathetic neurons. In contrast, transcription-dependent responses of PC12 cells to NGF such as priming and induction of the NGF-inducible large external glycoprotein, occurred despite the presence of Li ÷. SDS PAGE analysis of total cellular phosphoproteins (labeled by 2-h exposure to 32p_ orthophosphate) from neurite-bearing primed PC12 ceils revealed that Li ÷ reversibly inhibited the phosphorylation of a band of Mr 64,000 that was barely detectable in NGF-untreated PC12 cells. However, Li ÷ did not appear to affect the labeling of other phosphoproteins in either NGF-primed or untreated PC12 cultures, nor did it affect the rapid increase in phosphorylation of several proteins that occurs when NGF is first added to unprimed cultures. Several criteria indicated that the NGF-inducible phosphoprotein of Mr 64,000 is a microtubule-associated protein (MAP). Of the NGF-inducible phosphorylated MAPs that have been detected in PC12 cells (Mr 64,000, 72,000, 80,000, and 320,000), several (Mr 64,000, 72,000, and 80,000) were found to be substantially less phosphorylated in the presence of Li ÷. Neither a phorbol ester tumor promotor nor permeant cAMP analogs reversed the inhibitory effects of Li ÷ on neurite outgrowth or on phosphorylation of the component of Mr 64,000. Microtubules are a major and required constituent of neurites, and MAPs may regulate the assembly and stability of neuritic microtubules. The observation that Li ÷ selectively inhibits NGF-induced neurite outgrowth and MAP phosphorylation suggests a possible causal relationship between these two events.

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Section: Possible Mechanisms O[ the Inhibitory Action Of LI +mentioning

confidence: 99%

Lithium ion inhibits nerve growth factor-induced neurite outgrowth and phosphorylation of nerve growth factor-modulated microtubule-associated proteins.

Burstein¹,

Seeley²,

Greene³

1985

The Journal of Cell Biology

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“…for the PC 12 cell receptor subtypes (fNGFR: 10~8 to 1CT10 m ; s n g f r : 10-10 to 10~n m ; Schechter & Bothwell 1981;Bernd & Greene 1984;W oodruff & Neet 1986;H em pstead et al 1991;W eskam p & R eichardt 1991) make it unclear to w hat extent the n g f receptors on PC 12 cells are related to low-and high-affinity binding sites on prim ary neurons. Two n gf binding proteins have been identified: the fNGFR (also called p75 (Johnson et al 1986a;R adeke et al 1987)) and the trk tyrosine kinase (K aplan et al 1991a(K aplan et al , Kle 1991.…”

Section: Introductionmentioning

confidence: 99%

Mutation of tryptophan-21 in mouse nerve growth factor (NGF) affects binding to the fast NGF receptor but not induction of neurites on PC12 cells

1991

Proc. R. Soc. Lond. B

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By using in vitro DNA mutagenesis, we replaced the tryptophan residue at position 21 in mouse nerve growth factor (NGF) with either phenylalanine, leucine or serine. Yield, biological activity, immunological reactivity and receptor binding of the recombinant proteins were determined. All three mutants were produced at considerably lower yields than wild-type NGF, with the serine mutant being undetectable. The results of competitive binding assays show that tryptophan-21 is involved in recognition of the fast NGF receptor of PC12 cells. However, specific biological activity of NGF is not altered by the replacement of tryptophan-21. Our results therefore suggest that biological activity of NGF is not directly coupled to binding to the fast NGF receptor.

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“…The term (k a,i LR i À k d,i C i ) represents the net amounts of receptor and neurotrophin being converted into complex; v is the volume of the extracellular space. Equations ( 1) and ( 2) are similar to the ones used in experimental studies for analysing the cellular binding, internalization, and degradation of polypeptide ligands such as neurotrophins (Wiley & Cunningham 1981;Bernd & Greene 1984).…”

Section: The Model (A) Release and Removal Of Neurotrophinmentioning

confidence: 99%

“…In addition to increasing the number of synapses, NGF can enlarge the size of the presynaptic elements (Garofalo et al 1992). Neurotrophins may also be able to upregulate the density of their own receptors (Bernd & Greene 1984;Lindsay et al 1990;Holtzman et al 1992;Li et al 1995;ElShamy et al 1996;Ninkina et al 1996).…”

Section: (B) Axonal Growthmentioning

confidence: 99%

“…These are the values for the high a¤nity binding site, which mediates the biological response (Bothwell 1995) (Blo« chel & Thoenen 1995;Jeanpreª tre et al 1996). To show the e¡ects of changing ', in some of the simulations a higher or lower value was used; ( 2 days, based on growth of the amount of receptor (Bernd & Greene 1984). The value of v is 1X7 Â 10 À11 l.…”

Section: Units and Parameter Valuesmentioning

confidence: 99%

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Competition for neurotrophic factor in the development of nerve connections

Ooyen

Willshaw

1999

Proc. R. Soc. Lond. B

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The development of nerve connections is thought to involve competition among axons for survival promoting factors, or neurotrophins, which are released by the cells that are innervated by the axons. Although the notion of competition is widely used within neurobiology, there is little understanding of the nature of the competitive process and the underlying mechanisms. We present a new theoretical model to analyse competition in the development of nerve connections. According to the model, the precise manner in which neurotrophins regulate the growth of axons, in particular the growth of the amount of neurotrophin receptor, determines what patterns of target innervation can develop. The regulation of neurotrophin receptors is also involved in the degeneration and regeneration of connections. Competition in our model can be influenced by factors dependent on and independent of neuronal electrical activity. Our results point to the need to measure directly the specific form of the regulation by neurotrophins of their receptors.

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Association of 125I-nerve growth factor with PC12 pheochromocytoma cells. Evidence for internalization via high-affinity receptors only and for long-term regulation by nerve growth factor of both high- and low-affinity receptors.

Cited by 188 publications

References 49 publications

Lithium ion inhibits nerve growth factor-induced neurite outgrowth and phosphorylation of nerve growth factor-modulated microtubule-associated proteins.

Lithium ion inhibits nerve growth factor-induced neurite outgrowth and phosphorylation of nerve growth factor-modulated microtubule-associated proteins.

Mutation of tryptophan-21 in mouse nerve growth factor (NGF) affects binding to the fast NGF receptor but not induction of neurites on PC12 cells

Competition for neurotrophic factor in the development of nerve connections

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