Four novel interaction partners demonstrate diverse modulatory effects on voltage-gated CaV2.2 Ca2+ channels

Mallmann, Robert Theodor; Ondacova, Katarina; Moravcikova, Lucia; Jurkovičová-Tarabová, Bohumila; Pavlovicova, Michaela; Moravčík, Roman; Lichvarova, Lucia; Kominkova, Viera; Klugbauer, Norbert; Lacinová, Ľubica

doi:10.1007/s00424-018-02248-x

Cited by 5 publications

(12 citation statements)

References 51 publications

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“…Our screenings identified RTN1 as an interactor of domain IV of all three members of the Ca V 2-family. RTN1 demonstrates a broad expression in membranes of intracellular compartments with a higher density around the nuclei but also in the plasma membrane [45,52]. RTN1 is the only interactor of our YTH screenings that was also identified by a proteomic MS approach [42].…”

Section: Newly Identified Ca V 22 Interaction Partnersmentioning

confidence: 87%

“…Coexpression of the Grina/TMBIM3 protein together with the Ca V 2.2 channel decreased the peak Ca 2+ current density by approximately 54% [46] (see also Figure 3), i.e., to an extent comparable to those caused by coexpression of PTGDS (57%) and higher than that caused by coexpression of TMEM223 (67%) [45]. Negative modulatory effects of Grina/TMBIM3 on the Ca 2+ current were further enhanced by a shift of the voltage dependence of current activation toward more positive membrane potentials and by slowing the kinetics of current activation [46] (see also Figure 3).…”

Section: Modulation Of Ca V 22 Function By Novel Interaction Partnersmentioning

confidence: 90%

“…A large set of bait vectors encoding cDNA fragments of Ca V 2 Ca 2+ channel α1 subunits were constructed in our laboratory to identify, confirm, and characterize so far unknown Ca 2+ channel interaction partners [44][45][46]. The selection of bait constructs followed our aim to identify specific Ca V 2.2 interactors and to prove or to exclude the identified candidates as common Ca V 2-family interactors.…”

Section: Identification Of Ca V 22 Interaction Partnersmentioning

confidence: 99%

“…Most straightforward downregulation of calcium entry results from suppression of current amplitude. Such effect is caused by channel interaction with PTGDS, TMEM223, and Grina/TMBIM3 [45,46]. The negative effect of TMEM223 is further amplified by an increase in the extent of cumulative inactivation by an action potential train.…”

Section: Modulation Of Ca V 22 Function By Novel Interaction Partnersmentioning

confidence: 99%

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Modulation of voltage-gated Ca_V2.2 Ca²⁺ channels by newly identified interaction partners

et al. 2020

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Section: Newly Identified Ca V 22 Interaction Partnersmentioning

confidence: 87%

Section: Modulation Of Ca V 22 Function By Novel Interaction Partnersmentioning

confidence: 90%

Section: Identification Of Ca V 22 Interaction Partnersmentioning

confidence: 99%

Section: Modulation Of Ca V 22 Function By Novel Interaction Partnersmentioning

confidence: 99%

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Modulation of voltage-gated Ca_V2.2 Ca²⁺ channels by newly identified interaction partners

et al. 2020

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“…This binding is essential for channel tethering into presynaptic terminal. Another group used the yeast split-ubiquitin system to define the interactome of the Ca V 2.2 Ca 2+ channel α 1 subunit and identified tetraspanin-13 (TSPAN-13) (Mallmann et al 2013), reticulon 1 (RTN1), member 1 of solute carrier family 38 (SLC38), prostaglandin D2 synthase (PTGDS), and transmembrane protein 223 (TMEM223) (Mallmann et al 2019) as interaction partners of the channel. Detailed electrophysiological studies revealed that TSPAN-13, TMEM223, and, to a lesser extent, PTGDS and SLC38, negatively modulated Ca 2+ entry required for transmitter release and/or for dendritic plasticity under physiological conditions.…”

Section: Protein Complexes Formed By Ca V 22 Channelsmentioning

confidence: 99%

Structure, function and regulation of CaV2.2 N-type calcium channels

Jurkovičová-Tarabová

Lacinová²

2019

gpb

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N-type or Ca V 2.2 high-voltage activated calcium channels are distinguished by exclusively neuronal tissue distribution, sensitivity to ω-conotoxins, prominent inhibition by G-proteins, and a unique role in nociception. Most investigated modulatory pathway regulating the Ca V 2.2 channels is G-protein-coupled receptor-activated pathway leading to current inhibition by Gβγ subunit of G-protein. Binding of Gβγ dimer to α 1 subunit of the Ca V 2.2 channel transfers the channel form "willing" to "reluctant" gating state. Channel phosphorylation by protein kinase C potentiates N-type calcium current. Ca V 2.2 channels could be functionally regulated also by a number of protein-protein interactions. Ca V 2.2 null mice are hyposensitive to inflammatory and neuropathic pain, otherwise they have a mild phenotype. Consistent with the mild phenotype of the Ca V 2.2 -/mice, reports on mutations linked to a disease phenotype are scarce. Only one mutation related to human heritable diseases was identified until now. Pharmaceutical inhibition of Ca V 2.2 channels either by direct inhibition of the channel, by an activation of G-protein coupled receptors, or by inhibition of membrane targeting of the channel protein are promising strategies for treatment of severe chronic and/or neuropathic pain.

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Vestiges of the Bacterial Signal Recognition Particle-Based Protein Targeting in Mitochondria

Pyrih

Pánek

Durante

et al. 2021

Molecular Biology and Evolution

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The main bacterial pathway for inserting proteins into the plasma membrane relies on the signal recognition particle (SRP), composed of the Ffh protein and an associated RNA component, and the SRP-docking protein FtsY. Eukaryotes use an equivalent system of archaeal origin to deliver proteins into the endoplasmic reticulum, whereas a bacteria-derived SRP and FtsY function in the plastid. Here we report on the presence of homologs of the bacterial Ffh and FtsY proteins in various unrelated plastid-lacking unicellular eukaryotes, namely Heterolobosea, Alveida, Goniomonas, and Hemimastigophora. The monophyly of novel eukaryotic Ffh and FtsY groups, predicted mitochondrial localization experimentally confirmed for Naegleria gruberi, and a strong alphaproteobacterial affinity of the Ffh group, collectively suggest they constitute parts of an ancestral mitochondrial signal peptide-based protein-targeting system inherited from the last eukaryotic common ancestor, but lost from the majority of extant eukaryotes. The ability of putative signal peptides, predicted in a subset of mitochondrial-encoded N. gruberi proteins, to target a reporter fluorescent protein into the endoplasmic reticulum of Trypanosoma brucei, likely through their interaction with the cytosolic SRP, provided further support for this notion. We also illustrate that known mitochondrial ribosome-interacting proteins implicated in membrane protein targeting in opisthokonts (Mba1, Mdm38, and Mrx15) are broadly conserved in eukaryotes and non-redundant with the mitochondrial SRP system. Finally, we identified a novel mitochondrial protein (MAP67) present in diverse eukaryotes and related to the signal peptide-binding domain of Ffh, which may well be a hitherto unrecognized component of the mitochondrial membrane protein-targeting machinery.

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Four novel interaction partners demonstrate diverse modulatory effects on voltage-gated CaV2.2 Ca2+ channels

Cited by 5 publications

References 51 publications

Modulation of voltage-gated Ca_V2.2 Ca²⁺ channels by newly identified interaction partners

Modulation of voltage-gated Ca_V2.2 Ca²⁺ channels by newly identified interaction partners

Structure, function and regulation of CaV2.2 N-type calcium channels

Vestiges of the Bacterial Signal Recognition Particle-Based Protein Targeting in Mitochondria

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Four novel interaction partners demonstrate diverse modulatory effects on voltage-gated CaV2.2 Ca2+ channels

Cited by 5 publications

References 51 publications

Modulation of voltage-gated CaV2.2 Ca2+ channels by newly identified interaction partners

Modulation of voltage-gated CaV2.2 Ca2+ channels by newly identified interaction partners

Structure, function and regulation of CaV2.2 N-type calcium channels

Vestiges of the Bacterial Signal Recognition Particle-Based Protein Targeting in Mitochondria

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Product

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Modulation of voltage-gated Ca_V2.2 Ca²⁺ channels by newly identified interaction partners

Modulation of voltage-gated Ca_V2.2 Ca²⁺ channels by newly identified interaction partners