Functional Interaction between the Scaffold Protein Kidins220/ARMS and Neuronal Voltage-Gated Na+ Channels

Cesca, Fabrizia; Satapathy, Annyesha; Ferrea, Enrico; Nieus, Thierry; Benfenati, Fabio; Scholz‐Starke, Joachim

doi:10.1074/jbc.m115.654699

Cited by 14 publications

(18 citation statements)

References 41 publications

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“…All antibodies were affinity‐purified rabbit polyclonal antisera raised against synthetic peptides corresponding to the intracellular loop between domains I and II of rat Na v 1.1 and Na v 1.2, and between domains II and III of rat Na v 1.6 (Table ). Validation of all three Na v antibodies from Alomone has been demonstrated (Alomone; Cheng et al, ; Blanchard et al, ; Cesca et al, ; Liu, Tan, Xiao, & Dawe, ). Antibody specificity was confirmed using immunoblotting and immunocytochemistry of primary neurons and HEK cells as described below.…”

Section: Methodsmentioning

confidence: 99%

Sodium channel subtypes are differentially localized to pre‐ and post‐synaptic sites in rat hippocampus

Johnson

Herold

Milner

et al. 2017

J of Comparative Neurology

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Voltage-gated Na+ channels (Nav) modulate neuronal excitability, but the roles of the various Nav subtypes in specific neuronal functions such as synaptic transmission are unclear. We investigated expression of the three major brain Nav subtypes (Nav 1.1, Nav 1.2, Nav 1.6) in area CA1 and dentate gyrus of rat hippocampus. Using light and electron microscopy, we found labeling for all three Nav subtypes on dendrites, dendritic spines, and axon terminals, but the proportion of pre- and post-synaptic labeling for each subtype varied within and between subregions of CA1 and dentate gyrus. In the central hilus (CH) of the dentate gyrus, Nav 1.1 immunoreactivity was selectively expressed in presynaptic profiles, while Nav 1.2 and Nav 1.6 were expressed both pre- and post-synaptically. In contrast, in the stratum radiatum (SR) of CA1, Nav 1.1, Nav 1.2, and Nav 1.6 were selectively expressed in postsynaptic profiles. We next compared differences in Nav subtype expression between CH and SR axon terminals and between CH and SR dendrites and spines. Nav 1.1 and Nav 1.2 immunoreactivity was preferentially localized to CH axon terminals compared to SR, and in SR dendrites and spines compared to CH. No differences in Nav 1.6 immunoreactivity was found between axon terminals of CH and SR or between dendrites and spines of CH and SR. All Nav subtypes in both CH and SR were preferentially associated with asymmetric synapses rather than symmetric synapses. These findings indicate selective presynaptic and postsynaptic Nav expression in glutamatergic synapses of CH and SR supporting neurotransmitter release and synaptic plasticity.

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Section: Methodsmentioning

confidence: 99%

Sodium channel subtypes are differentially localized to pre‐ and post‐synaptic sites in rat hippocampus

Johnson

Herold

Milner

et al. 2017

J of Comparative Neurology

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“…Human embryonic kidney cells (HEK293, purchased from American Type Culture Collection) and primary cortical cultures from wild-type C57Bl/6 mice (Charles River, Calco, Italy) were prepared and maintained following standard procedures (Baldelli et al, 2007;Cesca et al, 2015).…”

Section: Cell Culture Proceduresmentioning

confidence: 99%

“…Immunohistochemistry on fixed cells was performed following standard procedures (Cesca et al, 2015). Coverslips were imaged by confocal microscopy (SP8, Leica Microsystems GmbH, Wetzlar, Germany) using a 63× (1.4 NA) magnification lens.…”

Section: Immunofluorescence and Confocal Microscopymentioning

confidence: 99%

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Neuronal hyperactivity causes Na+/H+ exchanger-induced extracellular acidification at active synapses

Chiacchiaretta

Latifi

Bramini

et al. 2017

Journal of Cell Science

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Extracellular pH impacts on neuronal activity, which is in turn an important determinant of extracellular H + concentration. The aim of this study was to describe the spatio-temporal dynamics of extracellular pH at synaptic sites during neuronal hyperexcitability. To address this issue we created ex.E 2 GFP, a membrane-targeted extracellular ratiometric pH indicator that is exquisitely sensitive to acidic shifts. By monitoring ex.E 2 GFP fluorescence in real time in primary cortical neurons, we were able to quantify pH fluctuations during network hyperexcitability induced by convulsant drugs or highfrequency electrical stimulation. Sustained hyperactivity caused a pH decrease that was reversible upon silencing of neuronal activity and located at active synapses. This acidic shift was not attributable to the outflow of synaptic vesicle H + into the cleft nor to the activity of membrane-exposed H + V-ATPase, but rather to the activity of the Na + /H + -exchanger. Our data demonstrate that extracellular synaptic pH shifts take place during epileptic-like activity of neural cultures, emphasizing the strict links existing between synaptic activity and synaptic pH. This evidence may contribute to the understanding of the physio-pathological mechanisms associated with hyperexcitability in the epileptic brain.

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“…Among other functions, ARMS has been implicated in the sustained activation of ERK1/2 in response to NGF (Arévalo et al, 2006(Arévalo et al, , 2004Hisata et al, 2007;Neubrand et al, 2010), in synaptic modulation (Arévalo et al, 2010;Cesca et al, 2015;Cortés et al, 2007;LopezMenendez et al, 2009;Sutachan et al, 2010;Wu et al, 2009), in dendritic arborization Chen et al, 2012;Wu et al, 2009), in excitotoxicity (Lopez-Menendez et al, 2009), in tumor progression in melanoma cells (Liao et al, 2011), in T cell activation (Deswal et al, 2013) and in the regulation of B cell development (Fiala et al, 2015). In addition, ARMS has been implicated in the secretion of the neurotensin hormone in BON cells, a cell line derived from a human pancreatic carcinoid tumor, in response to phorbol esters located downstream of PKD (Li et al, 2008(Li et al, , 2012.…”

Section: Introductionmentioning

confidence: 99%

ARMS/Kidins220 and synembryn-B levels regulate NGF-mediated secretion

López-Benito

Lillo

Hernández‐Hernández

et al. 2016

Journal of Cell Science

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Proper development of the nervous system requires a temporally and spatially orchestrated set of events including differentiation, synapse formation and neurotransmission. Nerve growth factor (NGF) acting through the TrkA neurotrophin receptor (also known as NTRK1) regulates many of these events. However, the molecular mechanisms responsible for NGF-regulated secretion are not completely understood. Here, we describe a new signaling pathway involving TrkA, ARMS (also known as Kidins220), synembryn-B and Rac1 in NGF-mediated secretion in PC12 cells. Whereas overexpression of ARMS blocked NGF-mediated secretion, without affecting basal secretion, a decrease in ARMS resulted in potentiation. Similar effects were observed with synembryn-B, a protein that interacts directly with ARMS. Downstream of ARMS and synembryn-B are Gαq and Trio proteins, which modulate the activity of Rac1 in response to NGF. Expression of dominant-negative Rac1 rescued the secretion defects of cells overexpressing ARMS or synembryn-B. Thus, this neurotrophin pathway represents a new mechanism responsible for NGF-regulated secretion.

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Functional Interaction between the Scaffold Protein Kidins220/ARMS and Neuronal Voltage-Gated Na+ Channels

Cited by 14 publications

References 41 publications

Sodium channel subtypes are differentially localized to pre‐ and post‐synaptic sites in rat hippocampus

Sodium channel subtypes are differentially localized to pre‐ and post‐synaptic sites in rat hippocampus

Neuronal hyperactivity causes Na+/H+ exchanger-induced extracellular acidification at active synapses

ARMS/Kidins220 and synembryn-B levels regulate NGF-mediated secretion

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