Neuronal Functions of Auxiliary Calcium Channel Subunits

Obermair, Gerald J.; Flucher, Bernhard E.

doi:10.1007/978-94-007-6334-0_2

Cited by 7 publications

(12 citation statements)

References 141 publications

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“…Therefore, we first need to question whether such unlimited subunit combinations are at all possible. A host of co-expression studies in heterologous cells support the concept of a great promiscuity in calcium channel subunit interactions (Obermair and Flucher, 2013 ). In fact, the authors of this review are not aware of a single study demonstrating that a given α 2 δ or β subunit cannot functionally interact with any specific Ca V 1 or Ca V 2 α 1 subunit, when heterologously co-expressed.…”

Section: Auxiliary Subunits Increase the Molecular Diversity Of Calcimentioning

confidence: 98%

“…There is also evidence that a similar heterogeneity in channel interactions occurs in differentiated and native cell systems (Obermair et al, ; Campiglio et al, ). In those cases where isolated channel combinations serve specific cellular functions this typically is linked to the co‐expression of a unique set of channel isoforms (Obermair and Flucher, ; Geisler et al, ).…”

Section: Auxiliary Subunits Increase the Molecular Diversity Of Calcimentioning

confidence: 99%

“…However, cell‐ and tissue‐specific expression patterns or differential developmental expression of the calcium channel subunit isoforms can limit the extent of possible subunit combinations in specific cell types (Obermair and Flucher, ; Geisler et al, ) . For example skeletal muscle exclusively expresses Ca V 1.1, α 2 δ‐1 and β 1a , whereas heart muscle expresses Ca V 1.2, α 2 δ‐1 and β 2b .…”

Section: Auxiliary Subunits Increase the Molecular Diversity Of Calcimentioning

confidence: 99%

“…Accordingly, null‐mutants of any of these dominant calcium channel subunit genes—in tottering (Ca V 2.1), ducky (α 2 δ‐2), and lethargic (β 4 ) mice—result in very similar neurological defects characterized by ataxia and cerebellar epilepsy (Felix, ). On the other hand, the majority of neurons in the central nervous system expresses multiple isoforms at comparable levels, allowing a great molecular diversity of calcium channel combinations and loss of a single isoform readily can be compensated by the other isoforms (Schlick et al, ; Obermair and Flucher, ; Geisler et al, ).…”

Section: Auxiliary Subunits Increase the Molecular Diversity Of Calcimentioning

confidence: 99%

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The Role of Auxiliary Subunits for the Functional Diversity of Voltage‐Gated Calcium Channels

Campiglio

Flucher

2015

Journal Cellular Physiology

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Voltage-gated calcium channels (VGCCs) represent the sole mechanism to convert membrane depolarization into cellular functions like secretion, contraction, or gene regulation. VGCCs consist of a pore-forming α1 subunit and several auxiliary channel subunits. These subunits come in multiple isoforms and splice-variants giving rise to a stunning molecular diversity of possible subunit combinations. It is generally believed that specific auxiliary subunits differentially regulate the channels and thereby contribute to the great functional diversity of VGCCs. If auxiliary subunits can associate and dissociate from pre-existing channel complexes, this would allow dynamic regulation of channel properties. However, most auxiliary subunits modulate current properties very similarly, and proof that any cellular calcium channel function is indeed modulated by the physiological exchange of auxiliary subunits is still lacking. In this review we summarize available information supporting a differential modulation of calcium channel functions by exchange of auxiliary subunits, as well as experimental evidence in support of alternative functions of the auxiliary subunits. At the heart of the discussion is the concept that, in their native environment, VGCCs function in the context of macromolecular signaling complexes and that the auxiliary subunits help to orchestrate the diverse protein–protein interactions found in these calcium channel signalosomes. Thus, in addition to a putative differential modulation of current properties, differential subcellular targeting properties and differential protein–protein interactions of the auxiliary subunits may explain the need for their vast molecular diversity. J. Cell. Physiol. 999: 00–00, 2015. © 2015 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. J. Cell. Physiol. 230: 2019–2031, 2015. © 2015 Wiley Periodicals, Inc.

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Section: Auxiliary Subunits Increase the Molecular Diversity Of Calcimentioning

confidence: 98%

Section: Auxiliary Subunits Increase the Molecular Diversity Of Calcimentioning

confidence: 99%

Section: Auxiliary Subunits Increase the Molecular Diversity Of Calcimentioning

confidence: 99%

Section: Auxiliary Subunits Increase the Molecular Diversity Of Calcimentioning

confidence: 99%

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The Role of Auxiliary Subunits for the Functional Diversity of Voltage‐Gated Calcium Channels

Campiglio

Flucher

2015

Journal Cellular Physiology

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“…On the one hand, neurons express a number of channel isoforms displaying distinct gating and current properties. On the other hand, single channels may be functionally distinct with respect to differential targeting to specific neuronal compartments, their interactions with auxiliary calcium channel subunits, or by the formation of macro-molecular complexes with specific up- and downstream signaling proteins (for review see [1, 2]). L-type voltage-dependent calcium channels (LTCCs) occupy a key position in the activity-dependent regulation of neuronal development and thereby in mediating different forms of synaptic plasticity and in activity-induced regulation of gene expression.…”

Section: Introductionmentioning

confidence: 99%

Regulation of Postsynaptic Stability by the L-type Calcium Channel Ca<sub>V</sub>1.3 and its Interaction with PDZ Proteins

Stanika¹,

Flucher²,

Obermair

2015

CMP

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Alterations in dendritic spine morphology and postsynaptic structure are a hallmark of neurological disorders. Particularly spine pruning of striatal medium spiny neurons and aberrant rewiring of corticostriatal synapses have been associated with the pathology of Parkinson’s disease and L-DOPA induced dyskinesia, respectively. Owing to its low activation threshold the neuronal L-type calcium channel CaV1.3 is particularly critical in the control of neuronal excitability and thus in the calcium-dependent regulation of neuronal functions. CaV1.3 channels are located in dendritic spines and contain a C-terminal class 1 PDZ domain-binding sequence. Until today the postsynaptic PDZ domain proteins shank, densin-180, and erbin have been shown to interact with CaV1.3 channels and to modulate their current properties. Interestingly experimental evidence suggests an involvement of all three PDZ proteins as well as CaV1.3 itself in regulating dendritic and postsynaptic morphology. Here we briefly review the importance of CaV1.3 and its proposed interactions with PDZ proteins for the stability of dendritic spines. With a special focus on the pathology associated with Parkinson’s disease, we discuss the hypothesis that CaV1.3 L-type calcium channels may be critical modulators of dendritic spine stability.

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L-type calcium channel blockers and substance P induce angiogenesis of cortical vessels associated with beta-amyloid plaques in an Alzheimer mouse model

Daschil

Kniewallner

Obermair

et al. 2015

Neurobiology of Aging

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It is well established that L-type calcium channels (LTCCs) are expressed in astroglia. However, their functional role is still speculative, especially under pathologic conditions. We recently showed that the α1 subunit-like immunoreactivity of the CaV1.2 channel is strongly expressed in reactive astrocytes around beta-amyloid plaques in 11-month-old Alzheimer transgenic (tg) mice with the amyloid precursor protein London and Swedish mutations. The aim of the present study was to examine the cellular expression of all LTCC subunits around beta-amyloid plaques by in situ hybridization using 35S-labeled oligonucleotides. Our data show that messenger RNAs (mRNAs) of the LTCC CaV1.2 α1 subunit as well as all auxiliary β and α2δ subunits, except α2δ-4, were expressed in the hippocampus of age-matched wild-type mice. It was unexpected to see, that cells directly located in the plaque core in the cortex expressed mRNAs for CaV1.2 α1, β2, β4, and α2δ-1, whereas no expression was detected in the halo. Furthermore, cells in the plaque core also expressed preprotachykinin-A mRNA, the precursor for substance P. By means of confocal microscopy, we demonstrated that collagen-IV-stained brain vessels in the cortex were associated with the plaque core and were immunoreactive for substance P. In cortical organotypic brain slices of adult Alzheimer mice, we could demonstrate that LTCC blockers increased angiogenesis, which was further potentiated by substance P. In conclusion, our data show that brain vessels associated with beta-amyloid plaques express substance P and an LTCC and may play a role in angiogenesis.

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Neuronal Functions of Auxiliary Calcium Channel Subunits

Cited by 7 publications

References 141 publications

The Role of Auxiliary Subunits for the Functional Diversity of Voltage‐Gated Calcium Channels

The Role of Auxiliary Subunits for the Functional Diversity of Voltage‐Gated Calcium Channels

Regulation of Postsynaptic Stability by the L-type Calcium Channel Ca<sub>V</sub>1.3 and its Interaction with PDZ Proteins

L-type calcium channel blockers and substance P induce angiogenesis of cortical vessels associated with beta-amyloid plaques in an Alzheimer mouse model

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