Annette Dolphin
YOU?
Author Swipe
View article: Biochemistry and physiology of voltage-gated calcium channel trafficking: a target for gabapentinoid drugs
Biochemistry and physiology of voltage-gated calcium channel trafficking: a target for gabapentinoid drugs Open
Voltage-gated calcium channels are multi-pass transmembrane proteins that have key features that are essential for their correct function. For example, the concerted movement of the voltage sensor domains in response to depolarization is r…
View article: Loss of the auxiliary α2δ1 voltage-sensitive calcium channel subunit impairs bone formation and anabolic responses to mechanical loading
Loss of the auxiliary α2δ1 voltage-sensitive calcium channel subunit impairs bone formation and anabolic responses to mechanical loading Open
Voltage-sensitive calcium channels (VSCCs) influence bone structure and function, including anabolic responses to mechanical loading. While the pore-forming (α1) subunit of VSCCs allows Ca2+ influx, auxiliary subunits regulate the biophysi…
View article: The Interplay Between Splicing of Two Exon Combinations Differentially Affects Membrane Targeting and Function of Human CaV2.2
The Interplay Between Splicing of Two Exon Combinations Differentially Affects Membrane Targeting and Function of Human CaV2.2 Open
N-type calcium channels (CaV2.2) are predominantly localized in presynaptic terminals, and are particularly important for pain transmission in the spinal cord. Furthermore, they have multiple isoforms, conferred by alternatively spliced or…
View article: The interplay between splicing of exons 18a and 47 differentially affects membrane targeting and function of human Ca<sub>V</sub>2.2
The interplay between splicing of exons 18a and 47 differentially affects membrane targeting and function of human Ca<sub>V</sub>2.2 Open
N-type calcium channels (Ca V 2.2) are predominantly localized in presynaptic terminals, and are particularly important for pain transmission in the spinal cord. Furthermore, they have multiple isoforms, conferred by alternatively-spliced …
View article: The importance of cache domains in α <sub>2</sub> δ proteins and the basis for their gabapentinoid selectivity
The importance of cache domains in α <sub>2</sub> δ proteins and the basis for their gabapentinoid selectivity Open
In this hybrid review, we have first collected and reviewed available information on the structure and function of the enigmatic cache domains in α2δ proteins. These are organized into two double cache (dCache_1) domains, and they are pres…
View article: Nerve injury increases native CaV2.2 trafficking in dorsal root ganglion mechanoreceptors
Nerve injury increases native CaV2.2 trafficking in dorsal root ganglion mechanoreceptors Open
Neuronal N-type (Ca V 2.2) voltage-gated calcium channels are essential for neurotransmission from primary afferent terminals in the dorsal horn. In this study, we have used a knockin mouse containing Ca V 2.2 with an inserted extracellula…
View article: Capsaicin-Induced Endocytosis of Endogenous Presynaptic CaV2.2 in DRG-Spinal Cord Co-Cultures Inhibits Presynaptic Function
Capsaicin-Induced Endocytosis of Endogenous Presynaptic CaV2.2 in DRG-Spinal Cord Co-Cultures Inhibits Presynaptic Function Open
The N-type calcium channel, CaV2.2 is key to neurotransmission from the primary afferent terminals of dorsal root ganglion (DRG) neurons to their postsynaptic targets in the spinal cord. In this study, we have utilized CaV2.2_HA knock-in m…
View article: Involvement of Ca<sub>V</sub>2.2 channels and α<sub>2</sub>δ‐1 in homeostatic synaptic plasticity in cultured hippocampal neurons
Involvement of Ca<sub>V</sub>2.2 channels and α<sub>2</sub>δ‐1 in homeostatic synaptic plasticity in cultured hippocampal neurons Open
In the mammalian brain, presynaptic Ca V 2 channels play a pivotal role in synaptic transmission by mediating fast neurotransmitter exocytosis via influx of Ca 2+ into the active zone of presynaptic terminals. However, the distribution and…
View article: Capsaicin-induced endocytosis of endogenous presynaptic Ca<sub>V</sub>2.2 in DRG-spinal cord co-cultures inhibits presynaptic function
Capsaicin-induced endocytosis of endogenous presynaptic Ca<sub>V</sub>2.2 in DRG-spinal cord co-cultures inhibits presynaptic function Open
The N-type calcium channel, Ca V 2.2 is key to neurotransmission from the primary afferent terminals of dorsal root ganglion (DRG) neurons to their post-synaptic targets in the spinal cord. In this study we have utilized Ca V 2.2_HA knock-…
View article: Involvement of Ca<sub>V</sub>2.2 channels and α<sub>2</sub>δ-1 in hippocampal homeostatic synaptic plasticity
Involvement of Ca<sub>V</sub>2.2 channels and α<sub>2</sub>δ-1 in hippocampal homeostatic synaptic plasticity Open
In the mammalian brain, presynaptic Ca V 2 channels play a pivotal role for synaptic transmission by mediating fast neurotransmitter exocytosis via influx of Ca 2+ into the active zone of presynaptic terminals. However, the distribution an…
View article: Proteolytic regulation of calcium channels - avoiding controversy.
Proteolytic regulation of calcium channels - avoiding controversy. Open
The publication of papers containing data obtained with suboptimal rigor in the experimental design and choice of key reagents, such as antibodies, can result in a lack of reproducibility and generate controversy that can both needlessly d…
View article: Amino acid sensor conserved from bacteria to humans
Amino acid sensor conserved from bacteria to humans Open
Significance Amino acids are the building blocks of life and important signaling molecules. Despite their common structure, no universal mechanism for amino acid recognition by cellular receptors is currently known. We discovered a simple …
View article: Biallelic <i>CACNA2D1</i> loss-of-function variants cause early-onset developmental epileptic encephalopathy
Biallelic <i>CACNA2D1</i> loss-of-function variants cause early-onset developmental epileptic encephalopathy Open
Voltage-gated calcium (CaV) channels form three subfamilies (CaV1–3). The CaV1 and CaV2 channels are heteromeric, consisting of an α1 pore-forming subunit, associated with auxiliary CaVβ and α2δ subunits. The α2δ subunits are encoded in ma…
View article: ADAM17 Mediates Proteolytic Maturation of Voltage-Gated Calcium Channel Auxiliary α2δ Subunits, and Enables Calcium Current Enhancement
ADAM17 Mediates Proteolytic Maturation of Voltage-Gated Calcium Channel Auxiliary α2δ Subunits, and Enables Calcium Current Enhancement Open
The auxiliary α2δ subunits of voltage-gated calcium (CaV) channels are key to augmenting expression and function of CaV1 and CaV2 channels, and are also important drug targets in several therapeutic areas, including neuropathic pain. The α…
View article: Rab11-dependent recycling of calcium channels is mediated by auxiliary subunit α2δ-1 but not α2δ-3
Rab11-dependent recycling of calcium channels is mediated by auxiliary subunit α2δ-1 but not α2δ-3 Open
N-type voltage-gated calcium channels (Ca V 2.2) are predominantly expressed at presynaptic terminals, and their function is regulated by auxiliary α 2 δ and β subunits. All four mammalian α 2 δ subunits enhance calcium currents through Ca…
View article: T-type Ca<sup>2+</sup>and persistent Na<sup>+</sup>currents synergistically elevate ventral, not dorsal, entorhinal cortical stellate cell excitability
T-type Ca<sup>2+</sup>and persistent Na<sup>+</sup>currents synergistically elevate ventral, not dorsal, entorhinal cortical stellate cell excitability Open
Summary The medial entorhinal cortex (mEC) plays a salient role in physiological processes such as spatial cognition and spatial coding. mEC layer II stellate neurons, in particular, influence these processes. Interestingly, ventral and do…
View article: Amino acid sensor conserved from bacteria to humans
Amino acid sensor conserved from bacteria to humans Open
Amino acids are recognized as signals by various receptors in bacteria, archaea, and eukaryotes. However, no common mechanism for amino acid recognition is currently known. Here we show that a subclass of a ubiquitous extracellular domain …
View article: Identification that ADAM17 mediates proteolytic maturation of calcium channel auxiliary α<sub>2</sub>δ subunits, and enables calcium current enhancement
Identification that ADAM17 mediates proteolytic maturation of calcium channel auxiliary α<sub>2</sub>δ subunits, and enables calcium current enhancement Open
The auxiliary α 2 δ subunits of voltage-gated calcium (Ca V ) channels are key to augmenting expression and function of Ca V 1 and Ca V 2 channels, and are also important drug targets in several therapeutic areas, including neuropathic pai…
View article: Rab11-dependent recycling of calcium channels is mediated by auxiliary subunit α<sub>2</sub>δ-1 but not α<sub>2</sub>δ-3
Rab11-dependent recycling of calcium channels is mediated by auxiliary subunit α<sub>2</sub>δ-1 but not α<sub>2</sub>δ-3 Open
N-type voltage-gated calcium channels (Ca V 2.2) are predominantly expressed at presynaptic terminals, and their function is regulated by auxiliary α 2 δ and β subunits. All four mammalian α 2 δ subunits enhance calcium currents through Ca…
View article: How Postdoctoral Research in Paul Greengard's Laboratory Shaped My Scientific Career, Although I Never Did Another Phosphorylation Assay
How Postdoctoral Research in Paul Greengard's Laboratory Shaped My Scientific Career, Although I Never Did Another Phosphorylation Assay Open
In this short review, I describe from personal experience how every step in the career of any scientist, no matter how disjointed and pragmatic each might seem at the time, will almost inevitably meld together, to help us all tackle novel …
View article: Functions of Presynaptic Voltage-gated Calcium Channels
Functions of Presynaptic Voltage-gated Calcium Channels Open
Voltage-gated calcium channels are the principal conduits for depolarization-mediated Ca2+ entry into excitable cells. In this review, the biophysical properties of the relevant members of this family of channels, those that are present in…
View article: FMRP regulates presynaptic localization of neuronal voltage gated calcium channels
FMRP regulates presynaptic localization of neuronal voltage gated calcium channels Open
Fragile X syndrome (FXS), the most common form of inherited intellectual disability and autism, results from the loss of fragile X mental retardation protein (FMRP). We have recently identified a direct interaction of FMRP with voltage-gat…
View article: IgGs from patients with amyotrophic lateral sclerosis and diabetes target Ca <sub>V</sub> α <sub>2</sub> δ1 subunits impairing islet cell function and survival
IgGs from patients with amyotrophic lateral sclerosis and diabetes target Ca <sub>V</sub> α <sub>2</sub> δ1 subunits impairing islet cell function and survival Open
Significance We provide evidence of a mechanistic link between ALS and T2DM. Our data show that a subgroup of ALS-T2DM patients have sera that enhance Ca V 1 channel-mediated Ca 2+ influx and exaggerate [Ca 2+ ] i . These effects occur bec…
View article: Disruption of the Key Ca2+ Binding Site in the Selectivity Filter of Neuronal Voltage-Gated Calcium Channels Inhibits Channel Trafficking
Disruption of the Key Ca2+ Binding Site in the Selectivity Filter of Neuronal Voltage-Gated Calcium Channels Inhibits Channel Trafficking Open
Voltage-gated calcium channels are exquisitely Ca2+ selective, conferred primarily by four conserved pore-loop glutamate residues contributing to the selectivity filter. There has been little previous work directly measuring whether the tr…
View article: Voltage-gated calcium channel blockers for psychiatric disorders: genomic reappraisal
Voltage-gated calcium channel blockers for psychiatric disorders: genomic reappraisal Open
Summary We reappraise the psychiatric potential of calcium channel blockers (CCBs). First, voltage-gated calcium channels are risk genes for several disorders. Second, use of CCBs is associated with altered psychiatric risks and outcomes. …
View article: Faculty Opinions recommendation of Presynaptic α2δ-2 Calcium Channel Subunits Regulate Postsynaptic GABAA Receptor Abundance and Axonal Wiring.
Faculty Opinions recommendation of Presynaptic α2δ-2 Calcium Channel Subunits Regulate Postsynaptic GABAA Receptor Abundance and Axonal Wiring. Open
Presynaptic ␣ 2 ␦ subunits of voltage-gated calcium channels regulate channel abundance and are involved in glutamatergic synapse formation.However, little is known about the specific functions of the individual ␣ 2 ␦ isoforms and their ro…
View article: Ablation of α <sub>2</sub> δ-1 inhibits cell-surface trafficking of endogenous N-type calcium channels in the pain pathway in vivo
Ablation of α <sub>2</sub> δ-1 inhibits cell-surface trafficking of endogenous N-type calcium channels in the pain pathway in vivo Open
Significance Neuronal N-type (Ca V 2.2) voltage-gated calcium channels are important at the first synapse in the pain pathway. In this study, we have characterized a knockin mouse containing Ca V 2.2 with an extracellular HA tag to determi…