bFGF Stimulates GAP-43 Phosphorylation at Ser41 and Modifies Its Intracellular Localization in Cultured Hippocampal Neurons

Tejero-Dı́ez, Pedro; Rodríguez-Sánchez, P; Martín-Cófreces, Noa B.; Díez‐Guerra, F. Javier

doi:10.1006/mcne.2000.0915

Cited by 31 publications

(30 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because the phosphorylation status of GAP-43 determines whether it will stabilize F-actin (phosphorylated GAP-43) or prevent F-actin polymerizing (unphosphorylated GAP-43; see introductory remarks) (He et al, 1997;Rosner and Vacun, 1999), we hypothesize that the effects on phosphorylation and F-actin are causally related. However, we cannot rule out that unphosphorylated GAP-43 also has indirect effects on F-actin via phosphatidyl inositol bis phosphate, which also contribute to the phenotype Tejero-Diez et al, 2000).…”

Section: Discussionmentioning

confidence: 92%

“…Moreover, elimination of GAP-43 blocked neurite outgrowth stimulated by either CAMs or bFGF, indicating its centrality in mediating the effects of IgSF-type CAMs, at least in vitro . Interestingly, bFGF-mediated stimulation of GAP-43 phosphorylation also increased its association with the actin cytoskeleton (Tejero-Diez et al, 2000). Hence, the disruption in selective fasciculation suggests that one component of the GAP-43 phenotype may be failure to transduce CAMmediated signals.…”

Section: Discussionmentioning

confidence: 98%

“…IgSF members, notably L1CAM and neural cell adhesion molecule (NCAM), as well as basic FGF (bFGF), stimulate GAP-43 phosphorylation in growth cones Tejero-Diez et al, 2000). Moreover, elimination of GAP-43 blocked neurite outgrowth stimulated by either CAMs or bFGF, indicating its centrality in mediating the effects of IgSF-type CAMs, at least in vitro .…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Growth-Associated Protein-43 Is Required for Commissural Axon Guidance in the Developing Vertebrate Nervous System

et al. 2002

View full text Add to dashboard Cite

Growth-associated protein-43 (GAP-43) is a major growth cone protein whose phosphorylation by PKC in response to extracellular guidance cues can regulate F-actin behavior. Here we show that 100% of homozygote GAP-43 (Ϫ/Ϫ) mice failed to form the anterior commissure (AC), hippocampal commissure (HC), and corpus callosum (CC) in vivo. Instead, although midline fusion was normal, selective fasciculation between commissural axons was inhibited, and TAG-1-labeled axons tangled bilaterally into Probst's bundles. Moreover, their growth cones had significantly smaller lamellas and reduced levels of F-actin in vitro. Likewise, 100% of GAP-43 (ϩ/Ϫ) mice with one disrupted allele also showed defects in HC and CC, whereas the AC was unaffected. Individual GAP-43 (ϩ/Ϫ) mice could be assigned to two groups based on the amount that PKC phosphorylation of GAP-43 was reduced in neocortical neurons. In mice with ϳ1% phosphorylation, the HC and CC were absent, whereas in mice with ϳ10% phosphorylation, the HC and CC were smaller. Both results suggest that PKC-mediated signaling in commissural axons may be defective. However, although Probst's bundles formed consistently at the location of the glial wedge, both GAP-43 (Ϫ/Ϫ) and GAP-43 (ϩ/ϩ) cortical axons were still repulsed by Slit-2 in vitro, precluding failure of this deflective signal from the glial wedge as the source of the phenotype. Nonetheless, the data show that a functional threshold of GAP-43 is required for commissure formation and suggests that failure to regulate F-actin in commissural growth cones may be related to inhibited PKC phosphorylation of GAP-43.

show abstract

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Growth-Associated Protein-43 Is Required for Commissural Axon Guidance in the Developing Vertebrate Nervous System

et al. 2002

View full text Add to dashboard Cite

show abstract

“…Growth-associated protein 43 (GAP43), required for neuronal development [58], is another conventional and novel PKC substrate that, similarly to MARCKS, normally localizes to the plasma membrane. Phosphorylation by PKC causes GAP43 to move away from the membrane [59], which promotes the disassociation of long actin filaments [60]. This phosphorylation also breaks GAP43's interaction with calmodulin [61,62].…”

Section: Regulation Of the Cytoskeleton: Marcks Gap43 And Taumentioning

confidence: 99%

Conventional protein kinase C in the brain: 40 years later

Callender

Newton

2017

Neuronal Signaling

View full text Add to dashboard Cite

Protein kinase C (PKC) is a family of enzymes whose members transduce a large variety of cellular signals instigated by the receptor-mediated hydrolysis of membrane phospholipids. While PKC has been widely implicated in the pathology of diseases affecting all areas of physiology including cancer, diabetes, and heart disease -it was discovered, and initially characterized, in the brain. PKC plays a key role in controlling the balance between cell survival and cell death. Its loss of function is generally associated with cancer, whereas its enhanced activity is associated with neurodegeneration. This review presents an overview of signaling by diacylglycerol (DG)-dependent PKC isozymes in the brain, and focuses on the role of the Ca 2 + -sensitive conventional PKC isozymes in neurodegeneration.

show abstract

“…38 Cultures were blocked for 1 h in 10% normal horse serum, 0.25% Triton X-100 in PBS and incubated overnight at 41C with mouse monoclonal antibodies against b-III-tubulin (1 : 1000; Sigma), GFAP (1 : 1000; Sigma), Nestin (1 : 500; Transduction Laboratories), vimentin (1 : 1000, Santa Cruz) and Map-2 (1 : 1000; Sigma) or monoclonal rat antibodies against BrdU (1 : 500; Abcam, UK) or rabbit antiserum against Ki-67 (1 : 3000; Lab Vision, UK), cleaved caspase-3 (1 : 100; Cell Signaling) synapsin-I (1 : 500; Chemicon) and GFAP (1 : 2000; DakoCytomation, Denmark).…”

Section: Icc and Immunoblotting (Wb)mentioning

confidence: 99%

Bcl-XL modulates the differentiation of immortalized human neural stem cells

et al. 2007

View full text Add to dashboard Cite

Understanding basic processes of human neural stem cell (hNSC) biology and differentiation is crucial for the development of cell replacement therapies. Bcl-X L has been reported to enhance dopaminergic neuron generation from hNSCs and mouse embryonic stem cells. In this work, we wanted to study, at the cellular level, the effects that Bcl-X L may exert on cell death during differentiation of hNSCs, and also on cell fate decisions and differentiation. To this end, we have used both v-myc immortalized (hNS1 cell line) and non-immortalized neurosphere cultures of hNSCs. In culture, using different experimental settings, we have consistently found that Bcl-X L enhances neuron generation while precluding glia generation. These effects do not arise from a glia-to-neuron shift (changes in fate decisions taken by precursors) or by only cell death counteraction, but, rather, data point to Bcl-X L increasing proliferation of neuronal progenitors, and inhibiting the differentiation of glial precursors. In vivo, after transplantation into the aged rat striatum, Bcl-X L overexpressing hNS1 cells generated more neurons and less glia than the control ones, confirming the results obtained in vitro. These results indicate an action of Bcl-X L modulating hNSCs differentiation, and may be thus important for the future development of cell therapy strategies for the diseased mammalian brain. The efficient generation of human neurons and glia from stem cells is the object of intense investigation, in the context of basic and preclinical cell replacement research. 1,2 Different means of genetic and epigenetic manipulations of stem cell cultures are being tested, aiming at enhancing their ability to generate the desired cell types. [3][4][5][6] In previous studies, we and others have demonstrated that Bcl-X L overexpression has a major impact on the generation of dopaminergic neurons from human neural stem cells (hNSCs) and mouse embryonic stem cells (mES). 7,8 Also, recent data from conditional Bcl-X L mutant mice add support to these observations. 9,10 In the present study, we are extending these observations and analyzing in detail the effects of Bcl-X L on hNSCs differentiation, focusing on precursor cell fate choices, cell death, and precursor proliferation.Bcl-X L is the most potent antiapoptotic protein among Bcl-2 family members, both in vitro and in vivo. 11-14 More specifically, Bcl-X L is essential for neuronal survival during brain development and in the adult central nervous system (CNS) (knockout mice and gene-expression studies 15,16 ). In addition to its antiapoptotic role, recent studies have described new roles of Bcl-X L in cell physiology -effects on Ca 2 þ homeostasis and gene expression 17 and synaptic transmission regulation 18 -under not necessarily apoptotic conditions. Several other studies have also described the role of Bcl-X L in the control of cell cycle, 19,20 a process well known to be tightly linked to progression of precursor cells toward neuronal and glia differentiation. 21,22 In this work, we aimed...

show abstract

bFGF Stimulates GAP-43 Phosphorylation at Ser41 and Modifies Its Intracellular Localization in Cultured Hippocampal Neurons

Cited by 31 publications

References 68 publications

Growth-Associated Protein-43 Is Required for Commissural Axon Guidance in the Developing Vertebrate Nervous System

Growth-Associated Protein-43 Is Required for Commissural Axon Guidance in the Developing Vertebrate Nervous System

Conventional protein kinase C in the brain: 40 years later

Bcl-XL modulates the differentiation of immortalized human neural stem cells

Contact Info

Product

Resources

About