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Query: UMLS:C0030567 (
Parkinson's disease
)
63,064
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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 LDOPA 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.
...
PMID:Regulation of Postsynaptic Stability by the L-type Calcium Channel CaV1.3 and its Interaction with PDZ Proteins. 2596 96
Dendritic spines are the postsynaptic compartments of glutamatergic synapses in the brain. Their number and shape are subject to change in synaptic plasticity and neurological disorders including autism spectrum disorders and
Parkinson's disease
. The L-type calcium channel Ca
V
1.3 constitutes an important calcium entry pathway implicated in the regulation of spine morphology. Here we investigated the importance of full-length Ca
V
1.3
L
and two C-terminally truncated splice variants (Ca
V
1.3
42A
and Ca
V
1.3
43S
) and their modulation by
densin-180
and shank1b for the morphology of dendritic spines of cultured hippocampal neurons. Live-cell immunofluorescence and super-resolution microscopy of epitope-tagged Ca
V
1.3
L
revealed its localization at the base-, neck-, and head-region of dendritic spines. Expression of the short splice variants or deletion of the C-terminal PDZ-binding motif in Ca
V
1.3
L
induced aberrant dendritic spine elongation. Similar morphological alterations were induced by co-expression of
densin-180
or shank1b with Ca
V
1.3
L
and correlated with increased Ca
V
1.3 currents and dendritic calcium signals in transfected neurons. Together, our findings suggest a key role of Ca
V
1.3 in regulating dendritic spine structure. Under physiological conditions it may contribute to the structural plasticity of glutamatergic synapses. Conversely, altered regulation of Ca
V
1.3 channels may provide an important mechanism in the development of postsynaptic aberrations associated with neurodegenerative disorders.
...
PMID:Splice variants of the Ca
V
1.3 L-type calcium channel regulate dendritic spine morphology. 2770 93
