title: Splice variants of the CaV1.3 L-type calcium channel regulate dendritic spine morphology.
abstract: 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 CaV1.3 constitutes an important calcium entry pathway implicated in the regulation of spine morphology. Here we investigated the importance of full-length CaV1.3Land two C-terminally truncated splice variants (CaV1.342Aand CaV1.343S) 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 CaV1.3Lrevealed 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 CaV1.3Linduced aberrant dendritic spine elongation. Similar morphological alterations were induced by co-expression of densin-180 or shank1b with CaV1.3Land correlated with increased CaV1.3 currents and dendritic calcium signals in transfected neurons. Together, our findings suggest a key role of CaV1.3 in regulating dendritic spine structure. Under physiological conditions it may contribute to the structural plasticity of glutamatergic synapses. Conversely, altered regulation of CaV1.3 channels may provide an important mechanism in the development of postsynaptic aberrations associated with neurodegenerative disorders.
authors.affiliation: Division of Physiology, Medical University Innsbruck, 6020 Innsbruck, Austria.
authors.forename: Ruslan
authors.initials: R
authors.lastname: Stanika
authors.affiliation: Division of Physiology, Medical University Innsbruck, 6020 Innsbruck, Austria.
authors.forename: Marta
authors.initials: M
authors.lastname: Campiglio
authors.affiliation: Department of Pharmacology and Toxicology, University of Innsbruck, 6020 Innsbruck, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Pinggera
authors.affiliation: Department of Molecular Physiology and Biophysics, Otolaryngology Head-Neck Surgery, and Neurology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Lee
authors.affiliation: Department of Pharmacology and Toxicology, University of Innsbruck, 6020 Innsbruck, Austria.
authors.forename: Jörg
authors.initials: J
authors.lastname: Striessnig
authors.affiliation: Division of Physiology, Medical University Innsbruck, 6020 Innsbruck, Austria.
authors.forename: Bernhard E
authors.initials: BE
authors.lastname: Flucher
authors.affiliation: Division of Physiology, Medical University Innsbruck, 6020 Innsbruck, Austria.
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Obermair
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D020746:Calcium Channels, L-Type / Q000096:biosynthesis* / Q000235:genetics; D049229:Dendritic Spines / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000235:genetics; D013569:Synapses / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: C485995:Cacna1d protein, mouse; D020746:Calcium Channels, L-Type; C504462:Lrrc7 protein, mouse; D009419:Nerve Tissue Proteins; C512412:SHANK1 protein, mouse; D012795:Sialoglycoproteins