Insulin receptor in Aplysia neurons: characterization, molecular cloning, and modulation of ion currents

Jonas, E.; Knox, R.; Kaczmarek, L. K.; Schwartz, JH; Solomon, D. H.

doi:10.1523/jneurosci.16-05-01645.1996

Cited by 78 publications

(63 citation statements)

References 62 publications

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“…PKC is activated by stimulation of the input to the BCNs (Wayne et al, 1999) and also by binding of insulin to its receptor, which modulates both ion currents and neurosecretion (Jonas et al, 1996;Sossin et al, 1996). In other cell types, such as adipocytes, the binding of insulin to its receptor activates the translocation of the glucose transporter (GLUT4) from an intracellular vesicle to the plasma membrane (Watson et al, 2004), possibly after rapidly occurring actin remodeling (Muallem et al, 1995;Lang et al, 2000;Tong et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…BCNs contain two physiologically characterized calcium channels (Ca V 1, Ca V 2), one of which (Ca V 2) is normally localized to intracellular vesicles and is sensitive to PKC (White et al, 1998). Activation of PKC with phorbol esters or diacylglycerols rapidly and reproducibly enhances voltage dependent calcium current by twofold to threefold (DeRiemer et al, 1985;Strong et al, 1987;Jonas et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

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PKC-Induced Intracellular Trafficking of Ca_V2 Precedes Its Rapid Recruitment to the Plasma Membrane

Zhang

Helm²,

Senatore³

et al. 2008

J. Neurosci.

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Activation of protein kinase C (PKC) potentiates secretion in Aplysia peptidergic neurons, in part by inducing new sites for peptide release at growth cone terminals. The mechanisms by which ion channels are trafficked to such sites are, however, not well understood. We now show that PKC activation rapidly recruits new Ca V 2 subunits to the plasma membrane, and that recruitment is blocked by latrunculin B, an inhibitor of actin polymerization. In contrast, inhibition of microtubule polymerization selectively prevents the appearance of Ca V 2 subunits only at the distal edge of the growth cone. In resting neurons, Ca V 2-containing organelles reside in the central region of growth cones, but are absent from distal lamellipodia. After activation of PKC, these organelles are transported on microtubules to the lamellipodium. The ability to traffic to the most distal sites of channel insertion inside the lamellipodium does, therefore, not require intact actin but requires intact microtubules. Only after activation of PKC do Ca V 2 channels associate with actin and undergo insertion into the plasma membrane.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

PKC-Induced Intracellular Trafficking of Ca_V2 Precedes Its Rapid Recruitment to the Plasma Membrane

Zhang

Helm²,

Senatore³

et al. 2008

J. Neurosci.

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“…Tyrosine kinases directly phosphorylate ion channels to provide rapid regulation of neuronal excitability (11)(12)(13)(14)(15)(16)(17)(18). Tyrosine kinase activation by G protein-coupled receptors (19) also suppresses delayed rectifying potassium channels by phosphorylation of a tyrosine residue in the amino terminus of Kv1.2 (20).…”

mentioning

confidence: 99%

TrkB Activation by Brain-derived Neurotrophic Factor Inhibits the G Protein-gated Inward Rectifier Kir3 by Tyrosine Phosphorylation of the Channel

Rogalski

Appleyard

Pattillo

et al. 2000

Journal of Biological Chemistry

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G protein-activated inwardly rectifying potassium channels (Kir3) are widely expressed throughout the brain, and regulation of their activity modifies neuronal excitability and synaptic transmission. In this study, we show that the neurotrophin brain-derived neurotrophic factor (BDNF), through activation of TrkB receptors, strongly inhibited the basal activity of Kir3. This inhibition was subunit dependent as functional homomeric channels of either Kir3.1 or Kir3.4 were significantly inhibited, whereas homomeric channels composed of Kir3.2 were insensitive. The general tyrosine kinase inhibitors genistein, Gö 6976, and K252a but not the serine/threonine kinase inhibitor staurosporine blocked the BDNF-induced inhibition of the channel. BDNF was also found to directly stimulate channel phosphorylation because Kir3.1 immunoprecipitated from BDNFstimulated cells showed enhanced labeling by anti-phosphotyrosine-specific antibodies. The BDNF effect required specific tyrosine residues in the amino terminus of Kir3.1 and Kir3.4 channels. Mutations of either Tyr-12, Tyr-67, or both in Kir3.1 or mutation of either Tyr-32, Tyr-53, or both of Kir3.4 channels to phenylalanine significantly blocked the BDNF-induced inhibition. The insensitive Kir3.2 was made sensitive to BDNF by adding a tyrosine (D41Y) and a lysine (P32K) upstream to generate a phosphorylation site motif analogous to that present in Kir3.4. These results suggest that neurotrophin activation of TrkB receptors may physiologically control neuronal excitability by direct tyrosine phosphorylation of the Kir3.1 and Kir3.4 subunits of G protein-gated inwardly rectifying potassium channels.Neurotrophins are a family of growth factors that include nerve growth factor, BDNF, 1 NT3, and NT-4/5 (1) and activate receptor tyrosine kinases (Trk) to regulate neuronal survival and differentiation during brain development (2). Neurotrophins also rapidly modulate neuronal excitability to regulate synaptic plasticity in the hippocampus (3-7), plasticity of spinal cord neurons in models of chronic pain (8), and excitability of cortical neurons (9). The mechanisms of these neuronal effects on excitability are not yet known; however, BDNF was shown to rapidly modulate sodium channels in the CA1 region of the hippocampus (3) and to enhance synaptic currents in hippocampal postsynaptic neurons (6). These studies suggest that BDNF has direct effects on ion channel properties to modulate synaptic activity.The neurotrophin receptors are transmembrane tyrosine kinases, and BDNF activation of the TrkB receptor is known to initiate a cascade of phosphorylation events that activate a complex of signaling proteins (10). Tyrosine kinases directly phosphorylate ion channels to provide rapid regulation of neuronal excitability (11-18). Tyrosine kinase activation by G protein-coupled receptors (19) also suppresses delayed rectifying potassium channels by phosphorylation of a tyrosine residue in the amino terminus of Kv1.2 (20). Similarly, phosphorylation of serine residues in the amino terminus...

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“…The best characterized actions are those of the serine/threonine kinases activated by calcium or cyclic nucleotides, whose transient effects are terminated by dephosphorylation by protein phosphatases. More recently, tyrosine phosphorylation has been observed for various ligand-gated channels (Hopfield et al, 1988;Wang and Salter, 1994;Moss et al, 1995;Valenzuela et al, 1995) and voltagegated channels (Huang et al, 1993;Wilson and Kaczmarek, 1993;Lev et al, 1995;Holmes et al, 1996a,b;Jonas et al, 1996) and can alter channel activity and synaptic transmission (Llinas et al, 1997), but the physiological significance of this process is unproven. To examine the physiological role of tyrosine phosphorylation in modulating ion channels, we have been characterizing the properties of channels in identified neurons that are modulated by serotonin [5-hydroxytryptamine (5-HT)].…”

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confidence: 99%

Requirement for Tyrosine Phosphatase during Serotonergic Neuromodulation by Protein Kinase C

Catarsi

Drapeau

1997

J. Neurosci.

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Tyrosine kinases and phosphatases are abundant in the nervous system, where they signal cellular differentiation, mediate the responses to growth factors, and direct neurite outgrowth during development. Tyrosine phosphorylation can also alter ion channel activity, but its physiological significance remains unclear. In an identified leech mechanosensory neuron, the ubiquitous neuromodulator serotonin increases the activity of a cation channel by activating protein kinase C (PKC), resulting in membrane depolarization and modulation of the receptive field properties. We observed that the effects on isolated neurons and channels were blocked by inhibiting tyrosine phosphatases. Serotonergic stimulation of PKC thus activates a tyrosine phosphatase activity associated with the channels, which reverses their constitutive inhibition by tyrosine phosphorylation, representing a novel form of neuromodulation.

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Insulin receptor in Aplysia neurons: characterization, molecular cloning, and modulation of ion currents

Cited by 78 publications

References 62 publications

PKC-Induced Intracellular Trafficking of Ca_V2 Precedes Its Rapid Recruitment to the Plasma Membrane

PKC-Induced Intracellular Trafficking of Ca_V2 Precedes Its Rapid Recruitment to the Plasma Membrane

TrkB Activation by Brain-derived Neurotrophic Factor Inhibits the G Protein-gated Inward Rectifier Kir3 by Tyrosine Phosphorylation of the Channel

Requirement for Tyrosine Phosphatase during Serotonergic Neuromodulation by Protein Kinase C

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Insulin receptor in Aplysia neurons: characterization, molecular cloning, and modulation of ion currents

Cited by 78 publications

References 62 publications

PKC-Induced Intracellular Trafficking of CaV2 Precedes Its Rapid Recruitment to the Plasma Membrane

PKC-Induced Intracellular Trafficking of CaV2 Precedes Its Rapid Recruitment to the Plasma Membrane

TrkB Activation by Brain-derived Neurotrophic Factor Inhibits the G Protein-gated Inward Rectifier Kir3 by Tyrosine Phosphorylation of the Channel

Requirement for Tyrosine Phosphatase during Serotonergic Neuromodulation by Protein Kinase C

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PKC-Induced Intracellular Trafficking of Ca_V2 Precedes Its Rapid Recruitment to the Plasma Membrane

PKC-Induced Intracellular Trafficking of Ca_V2 Precedes Its Rapid Recruitment to the Plasma Membrane