Association of Cav1.3 L-type calcium channels with shank

Hua Zhang, Anton Maximov, Yu Fu, Fang Xu, Tie Shan Tang, Tatiana Tkatch, D. James Surmeier, Ilya Bezprozvanny

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

Neurons express multiple types of voltage-gated calcium (Ca2+) channels. Two subtypes of neuronal L-type Ca2+ channels are encoded by Cav1.2 and Cav1.3 pore-forming subunits. Both Ca v1.2 and Cav1.3 subunits contain class I PDZ (postsynaptic density-95/Discs large/zona occludens-1) domain-binding consensus at their C termini. In yeast two-hybrid screen of rat brain cDNA library with the C-terminal bait of Cav1.3a (long C-terminal splice variant) L-type Ca2+ channel subunit, we isolated multiple clones of postsynaptic adaptor protein Shank. We demonstrated a specific association of Ca v1.3a C termini, but not of Cav1.2 C termini, with Shank PDZ domain in vitro. We further demonstrated that the proline-rich region present in C termini of Cav1.3a subunit binds to Shank Src homology 3 domain. We established that Cav1.3a and Shank localized to postsynaptic locations in cultured rat hippocampal neurons. By expressing epitope-tagged recombinant Cav1.3 subunits in rat hippocampal neuronal cultures, we demonstrated that the presence of Shank-binding motifs in Cav1.3a sequence is both necessary and sufficient for synaptic clustering of Cav1.3 L-type Ca2+ channels. In experiments with dominant-negative peptides and dihydropyridine-resistant Cav1.3a mutants, we demonstrated an importance of Shank-binding motif in Ca v1.3a sequence for phosphorylated cAMP response element-binding protein (pCREB) signaling in cultured hippocampal neurons. Our results directly link Cav1.3 neuronal L-type Ca2+ channels to macromolecular signaling complex formed by Shank and other modular adaptor proteins at postsynaptic density and provide novel information about the role played by Cav1.3 L-type Ca2+ channels in pCREB signaling.

Original languageEnglish (US)
Pages (from-to)1037-1049
Number of pages13
JournalJournal of Neuroscience
Volume25
Issue number5
DOIs
StatePublished - Feb 2 2005

Fingerprint

L-Type Calcium Channels
Cyclic AMP Response Element-Binding Protein
Neurons
PDZ Domains
Macromolecular Substances
Post-Synaptic Density
src Homology Domains
Herpes Zoster
Calcium Channels
Gene Library
Proline
Cluster Analysis
Epitopes
Clone Cells
Yeasts
Peptides
Brain
Proteins

Keywords

  • Calcium channels
  • CREB
  • PDZ domains
  • Postsynaptic density
  • Protein targeting
  • Synapse
  • Synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Association of Cav1.3 L-type calcium channels with shank. / Zhang, Hua; Maximov, Anton; Fu, Yu; Xu, Fang; Tang, Tie Shan; Tkatch, Tatiana; Surmeier, D. James; Bezprozvanny, Ilya.

In: Journal of Neuroscience, Vol. 25, No. 5, 02.02.2005, p. 1037-1049.

Research output: Contribution to journalArticle

Zhang, H, Maximov, A, Fu, Y, Xu, F, Tang, TS, Tkatch, T, Surmeier, DJ & Bezprozvanny, I 2005, 'Association of Cav1.3 L-type calcium channels with shank', Journal of Neuroscience, vol. 25, no. 5, pp. 1037-1049. https://doi.org/10.1523/JNEUROSCI.4554-04.2005
Zhang, Hua ; Maximov, Anton ; Fu, Yu ; Xu, Fang ; Tang, Tie Shan ; Tkatch, Tatiana ; Surmeier, D. James ; Bezprozvanny, Ilya. / Association of Cav1.3 L-type calcium channels with shank. In: Journal of Neuroscience. 2005 ; Vol. 25, No. 5. pp. 1037-1049.
@article{7762cbaf22aa47fea67d4b292c9213ce,
title = "Association of Cav1.3 L-type calcium channels with shank",
abstract = "Neurons express multiple types of voltage-gated calcium (Ca2+) channels. Two subtypes of neuronal L-type Ca2+ channels are encoded by Cav1.2 and Cav1.3 pore-forming subunits. Both Ca v1.2 and Cav1.3 subunits contain class I PDZ (postsynaptic density-95/Discs large/zona occludens-1) domain-binding consensus at their C termini. In yeast two-hybrid screen of rat brain cDNA library with the C-terminal bait of Cav1.3a (long C-terminal splice variant) L-type Ca2+ channel subunit, we isolated multiple clones of postsynaptic adaptor protein Shank. We demonstrated a specific association of Ca v1.3a C termini, but not of Cav1.2 C termini, with Shank PDZ domain in vitro. We further demonstrated that the proline-rich region present in C termini of Cav1.3a subunit binds to Shank Src homology 3 domain. We established that Cav1.3a and Shank localized to postsynaptic locations in cultured rat hippocampal neurons. By expressing epitope-tagged recombinant Cav1.3 subunits in rat hippocampal neuronal cultures, we demonstrated that the presence of Shank-binding motifs in Cav1.3a sequence is both necessary and sufficient for synaptic clustering of Cav1.3 L-type Ca2+ channels. In experiments with dominant-negative peptides and dihydropyridine-resistant Cav1.3a mutants, we demonstrated an importance of Shank-binding motif in Ca v1.3a sequence for phosphorylated cAMP response element-binding protein (pCREB) signaling in cultured hippocampal neurons. Our results directly link Cav1.3 neuronal L-type Ca2+ channels to macromolecular signaling complex formed by Shank and other modular adaptor proteins at postsynaptic density and provide novel information about the role played by Cav1.3 L-type Ca2+ channels in pCREB signaling.",
keywords = "Calcium channels, CREB, PDZ domains, Postsynaptic density, Protein targeting, Synapse, Synaptic plasticity",
author = "Hua Zhang and Anton Maximov and Yu Fu and Fang Xu and Tang, {Tie Shan} and Tatiana Tkatch and Surmeier, {D. James} and Ilya Bezprozvanny",
year = "2005",
month = "2",
day = "2",
doi = "10.1523/JNEUROSCI.4554-04.2005",
language = "English (US)",
volume = "25",
pages = "1037--1049",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "5",

}

TY - JOUR

T1 - Association of Cav1.3 L-type calcium channels with shank

AU - Zhang, Hua

AU - Maximov, Anton

AU - Fu, Yu

AU - Xu, Fang

AU - Tang, Tie Shan

AU - Tkatch, Tatiana

AU - Surmeier, D. James

AU - Bezprozvanny, Ilya

PY - 2005/2/2

Y1 - 2005/2/2

N2 - Neurons express multiple types of voltage-gated calcium (Ca2+) channels. Two subtypes of neuronal L-type Ca2+ channels are encoded by Cav1.2 and Cav1.3 pore-forming subunits. Both Ca v1.2 and Cav1.3 subunits contain class I PDZ (postsynaptic density-95/Discs large/zona occludens-1) domain-binding consensus at their C termini. In yeast two-hybrid screen of rat brain cDNA library with the C-terminal bait of Cav1.3a (long C-terminal splice variant) L-type Ca2+ channel subunit, we isolated multiple clones of postsynaptic adaptor protein Shank. We demonstrated a specific association of Ca v1.3a C termini, but not of Cav1.2 C termini, with Shank PDZ domain in vitro. We further demonstrated that the proline-rich region present in C termini of Cav1.3a subunit binds to Shank Src homology 3 domain. We established that Cav1.3a and Shank localized to postsynaptic locations in cultured rat hippocampal neurons. By expressing epitope-tagged recombinant Cav1.3 subunits in rat hippocampal neuronal cultures, we demonstrated that the presence of Shank-binding motifs in Cav1.3a sequence is both necessary and sufficient for synaptic clustering of Cav1.3 L-type Ca2+ channels. In experiments with dominant-negative peptides and dihydropyridine-resistant Cav1.3a mutants, we demonstrated an importance of Shank-binding motif in Ca v1.3a sequence for phosphorylated cAMP response element-binding protein (pCREB) signaling in cultured hippocampal neurons. Our results directly link Cav1.3 neuronal L-type Ca2+ channels to macromolecular signaling complex formed by Shank and other modular adaptor proteins at postsynaptic density and provide novel information about the role played by Cav1.3 L-type Ca2+ channels in pCREB signaling.

AB - Neurons express multiple types of voltage-gated calcium (Ca2+) channels. Two subtypes of neuronal L-type Ca2+ channels are encoded by Cav1.2 and Cav1.3 pore-forming subunits. Both Ca v1.2 and Cav1.3 subunits contain class I PDZ (postsynaptic density-95/Discs large/zona occludens-1) domain-binding consensus at their C termini. In yeast two-hybrid screen of rat brain cDNA library with the C-terminal bait of Cav1.3a (long C-terminal splice variant) L-type Ca2+ channel subunit, we isolated multiple clones of postsynaptic adaptor protein Shank. We demonstrated a specific association of Ca v1.3a C termini, but not of Cav1.2 C termini, with Shank PDZ domain in vitro. We further demonstrated that the proline-rich region present in C termini of Cav1.3a subunit binds to Shank Src homology 3 domain. We established that Cav1.3a and Shank localized to postsynaptic locations in cultured rat hippocampal neurons. By expressing epitope-tagged recombinant Cav1.3 subunits in rat hippocampal neuronal cultures, we demonstrated that the presence of Shank-binding motifs in Cav1.3a sequence is both necessary and sufficient for synaptic clustering of Cav1.3 L-type Ca2+ channels. In experiments with dominant-negative peptides and dihydropyridine-resistant Cav1.3a mutants, we demonstrated an importance of Shank-binding motif in Ca v1.3a sequence for phosphorylated cAMP response element-binding protein (pCREB) signaling in cultured hippocampal neurons. Our results directly link Cav1.3 neuronal L-type Ca2+ channels to macromolecular signaling complex formed by Shank and other modular adaptor proteins at postsynaptic density and provide novel information about the role played by Cav1.3 L-type Ca2+ channels in pCREB signaling.

KW - Calcium channels

KW - CREB

KW - PDZ domains

KW - Postsynaptic density

KW - Protein targeting

KW - Synapse

KW - Synaptic plasticity

UR - http://www.scopus.com/inward/record.url?scp=13944250584&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=13944250584&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.4554-04.2005

DO - 10.1523/JNEUROSCI.4554-04.2005

M3 - Article

C2 - 15689539

AN - SCOPUS:13944250584

VL - 25

SP - 1037

EP - 1049

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 5

ER -