scholarly journals Fibroblast growth factor 14 is an intracellular modulator of voltage-gated sodium channels

2005 ◽  
Vol 569 (1) ◽  
pp. 179-193 ◽  
Author(s):  
Jun-Yang Lou ◽  
Fernanda Laezza ◽  
Benjamin R. Gerber ◽  
Maolei Xiao ◽  
Kathryn A. Yamada ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Sodium Channels ◽  
Fibroblast Growth ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels

scholarly journals Identification of Novel Interaction Sites that Determine Specificity between Fibroblast Growth Factor Homologous Factors and Voltage-gated Sodium Channels

2011 ◽  
Vol 286 (27) ◽  
pp. 24253-24263 ◽  
Author(s):  
Chaojian Wang ◽  
Chuan Wang ◽  
Ethan G. Hoch ◽  
Geoffrey S. Pitt
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Sodium Channels ◽  
Fibroblast Growth ◽  
Subcellular Targeting ◽  
Voltage Gated ◽  
Interaction Sites ◽  
Voltage Gated Sodium Channels ◽  
C Terminus ◽  
The Individual

Fibroblast growth factor homologous factors (FHFs, FGF11–14) bind to the C termini (CTs) of specific voltage-gated sodium channels (VGSC) and thereby regulate their function. The effect of an individual FHF on a specific VGSC varies greatly depending upon the individual FHF isoform. How individual FHFs impart distinctive effects on specific VGSCs is not known and the specificity of these pairwise interactions is not understood. Using several biochemical approaches combined with functional analysis, we mapped the interaction site for FGF12B on the NaV1.5 C terminus and discovered previously unknown determinants necessary for FGF12 interaction. Also, we demonstrated that FGF12B binds to some, but not all NaV1 CTs, suggesting specificity of interaction. Exploiting a human single nucleotide polymorphism in the core domain of FGF12 (P149Q), we identified a surface proline that contributes a part of this pairwise specificity. This proline is conserved among all FHFs, and mutation of the homologous residue in FGF13 also leads to loss of interaction with a specific VGSC CT (NaV1.1) and loss of modulation of the resultant Na+ channel function. We hypothesized that some of the specificity mediated by this proline may result from differences in the affinity of the binding partners. Consistent with this hypothesis, surface plasmon resonance data showed that the P149Q mutation decreased the binding affinity between FHFs and VGSC CTs. Moreover, immunocytochemistry revealed that the mutation prevented proper subcellular targeting of FGF12 to the axon initial segment in neurons. Together, these results give new insights into details of the interactions between FHFs and NaV1.x CTs, and the consequent regulation of Na+ channels.

scholarly journals Fibroblast Growth Factor Homologous Factors Control Neuronal Excitability through Modulation of Voltage-Gated Sodium Channels

Neuron ◽  
2007 ◽  
Vol 55 (3) ◽  
pp. 449-463 ◽  
Author(s):  
Mitchell Goldfarb ◽  
Jon Schoorlemmer ◽  
Anthony Williams ◽  
Shyam Diwakar ◽  
Qing Wang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Sodium Channels ◽  
Neuronal Excitability ◽  
Fibroblast Growth ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels

scholarly journals Differential modulation of voltage-gated sodium channels by nerve growth factor in three major subsets of TrkA-expressing nociceptors

2018 ◽  
Vol 14 ◽  
pp. 174480691881464 ◽  
Author(s):  
Irina Schaefer ◽  
Vincenzo Prato ◽  
Alice Arcourt ◽  
Francisco J Taberner ◽  
Stefan G Lechner
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Sodium Channels ◽  
Differential Modulation ◽  
Nerve Growth ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels

scholarly journals The Fibroblast Growth Factor 14·Voltage-gated Sodium Channel Complex Is a New Target of Glycogen Synthase Kinase 3 (GSK3)

2013 ◽  
Vol 288 (27) ◽  
pp. 19370-19385 ◽  
Author(s):  
Alexander S. Shavkunov ◽  
Norelle C. Wildburger ◽  
Miroslav N. Nenov ◽  
Thomas F. James ◽  
Tetyana P. Buzhdygan ◽  
...  
Keyword(s):  
Growth Factor ◽  
Sodium Channel ◽  
Fibroblast Growth Factor ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Fibroblast Growth ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated

Elucidating the Role of Val-Asn 95 and Arg-Gly 52 Mutations on Structure and Stability of Fibroblast Growth Factor Homologous Factor 2

2019 ◽  
Vol 26 (11) ◽  
pp. 848-859
Author(s):  
Vidyalatha Kolli ◽  
Subhankar Paul ◽  
Praveen Kumar Guttula ◽  
Nandini Sarkar
Keyword(s):  
Amino Acids ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Signal Sequence ◽  
Fibroblast Growth ◽  
Structure And Stability ◽  
Secretion Signal ◽  
Acrylamide Quenching ◽  
Voltage Gated Sodium Channels

Background: Fibroblast growth Factor Homologous Factors (FHFs) belong to a subclass of Fibroblast Growth Factor (FGF) family owing to their high sequence and structural similarities with FGFs. However, despite these similarities, there are properties which set them apart from FGFs. FHFs lack the secretion signal sequence unlike other FGF members, except FGF1 and 2. Unlike FGFs, FHFs are not able to bind to FGF Receptors (FGFRs) and instead have been implicated in binding to Voltage-Gated Sodium Channels (VGSCs), neuronal MAP kinase scaffold protein and islet-brain-2 (IB2). The two amino acids Arg-52 and Val95 are conserved in all FHFs and mutation of these residues lead to its inability to bind with VGSC/IB2. However, it is not clear whether the loss of binding is due to destabilization of the protein on mutation or due to involvement of Arg52 and Val95 in conferring functionality to FHFs. Objective: In the present study, we have mutated these two conserved residues of FHF2 with its corresponding FGF counterpart amino acids and studied the effects of the mutations on the structure and stability of the protein. Methods: Several biophysical methods like isothermal equilibrium denaturation study, ANS fluorescence, intrinsic fluorescence, acrylamide quenching, circular dichroism studies as well as using computational approaches were employed. Results: The single mutations were found to affect the overall stability, conformation and functionality of the protein. Conclusion: Thus, the studies throw light on the role of specific amino acids in deciding the stability, structure and functionality of proteins and will be useful for development of therapeutically engineered proteins.

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