Key role of the postsynaptic density scaffold proteins Shank and Homer in the functional architecture of Ca2+ homeostasis at dendritic spines in hippocampal neurons

Carlo Sala, Gautier Roussignol, Jacopo Meldolesi, Laurent Fagni

Research output: Contribution to journalArticle

Abstract

A key aspect of postsynaptic function, also important for plasticity, is the segregation within dendritic spines of Ca2+ rises attributable to release from intracellular stores. Previous studies have shown that overexpression in hippocampal neurons of two postsynaptic density (PSD) scaffold proteins, Shank1B and Homer1b, induces spine maturation, including translocation of the intracellular Ca2+ channel inositol trisphosphate receptor (IP3R). The structural and functional significance of these processes remained undefined. Here, we show that in its relocation, IP3R is accompanied by other endoplasmic reticulum (ER) proteins: the Ca2+ pump sarcoendoplasmic reticulum calcium ATPase, the lumenal Ca2+-binding protein calreticulin, the ER lumen-addressed green fluorescent protein, and, to a lesser extent, the membrane chaperone calbindin. The specificity of these translocations was demonstrated by their inhibition by both a Shank1 fragment and the dominant-negative Homer1a. Activation in Shank1B-transfected neurons of the metabotropic glutamatergic receptors 1/5 (mGluRs1/5), which induce IP3 generation with ensuing Ca2+ release from the stores, triggered considerable increases in Ca2+-dependent responses: activation of the big K+ channel, which was revealed by patch clamping, and extracellular signal-regulated protein kinase (ERK) phosphorylation. The interaction of Shank1B and Homer1b appears as the molecular mechanism linking mGluRs1/5, strategically located in the spines, to IP3R with the integration of entire ER cisternas in the PSD and with consequences on both local Ca 2+ homeostasis and overall neuronal signaling.

Original languageEnglish
Pages (from-to)4587-4592
Number of pages6
JournalJournal of Neuroscience
Volume25
Issue number18
DOIs
Publication statusPublished - May 4 2005

Fingerprint

Dendritic Spines
Endoplasmic Reticulum
Homeostasis
Neurons
Spine
Calreticulin
Large-Conductance Calcium-Activated Potassium Channels
Post-Synaptic Density
Calbindins
Reticulum
Calcium-Transporting ATPases
Extracellular Signal-Regulated MAP Kinases
Inositol
Green Fluorescent Proteins
Constriction
Protein Kinases
Carrier Proteins
Phosphorylation
Membranes
postsynaptic density proteins

Keywords

  • Big K channel
  • ER calcium stores
  • ERK1/2
  • Homer
  • mGluR
  • Postsynaptic density
  • Shank

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Key role of the postsynaptic density scaffold proteins Shank and Homer in the functional architecture of Ca2+ homeostasis at dendritic spines in hippocampal neurons. / Sala, Carlo; Roussignol, Gautier; Meldolesi, Jacopo; Fagni, Laurent.

In: Journal of Neuroscience, Vol. 25, No. 18, 04.05.2005, p. 4587-4592.

Research output: Contribution to journalArticle

@article{27ffd04b15e840eca975b7748f8113cc,
title = "Key role of the postsynaptic density scaffold proteins Shank and Homer in the functional architecture of Ca2+ homeostasis at dendritic spines in hippocampal neurons",
abstract = "A key aspect of postsynaptic function, also important for plasticity, is the segregation within dendritic spines of Ca2+ rises attributable to release from intracellular stores. Previous studies have shown that overexpression in hippocampal neurons of two postsynaptic density (PSD) scaffold proteins, Shank1B and Homer1b, induces spine maturation, including translocation of the intracellular Ca2+ channel inositol trisphosphate receptor (IP3R). The structural and functional significance of these processes remained undefined. Here, we show that in its relocation, IP3R is accompanied by other endoplasmic reticulum (ER) proteins: the Ca2+ pump sarcoendoplasmic reticulum calcium ATPase, the lumenal Ca2+-binding protein calreticulin, the ER lumen-addressed green fluorescent protein, and, to a lesser extent, the membrane chaperone calbindin. The specificity of these translocations was demonstrated by their inhibition by both a Shank1 fragment and the dominant-negative Homer1a. Activation in Shank1B-transfected neurons of the metabotropic glutamatergic receptors 1/5 (mGluRs1/5), which induce IP3 generation with ensuing Ca2+ release from the stores, triggered considerable increases in Ca2+-dependent responses: activation of the big K+ channel, which was revealed by patch clamping, and extracellular signal-regulated protein kinase (ERK) phosphorylation. The interaction of Shank1B and Homer1b appears as the molecular mechanism linking mGluRs1/5, strategically located in the spines, to IP3R with the integration of entire ER cisternas in the PSD and with consequences on both local Ca 2+ homeostasis and overall neuronal signaling.",
keywords = "Big K channel, ER calcium stores, ERK1/2, Homer, mGluR, Postsynaptic density, Shank",
author = "Carlo Sala and Gautier Roussignol and Jacopo Meldolesi and Laurent Fagni",
year = "2005",
month = "5",
day = "4",
doi = "10.1523/JNEUROSCI.4822-04.2005",
language = "English",
volume = "25",
pages = "4587--4592",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "18",

}

TY - JOUR

T1 - Key role of the postsynaptic density scaffold proteins Shank and Homer in the functional architecture of Ca2+ homeostasis at dendritic spines in hippocampal neurons

AU - Sala, Carlo

AU - Roussignol, Gautier

AU - Meldolesi, Jacopo

AU - Fagni, Laurent

PY - 2005/5/4

Y1 - 2005/5/4

N2 - A key aspect of postsynaptic function, also important for plasticity, is the segregation within dendritic spines of Ca2+ rises attributable to release from intracellular stores. Previous studies have shown that overexpression in hippocampal neurons of two postsynaptic density (PSD) scaffold proteins, Shank1B and Homer1b, induces spine maturation, including translocation of the intracellular Ca2+ channel inositol trisphosphate receptor (IP3R). The structural and functional significance of these processes remained undefined. Here, we show that in its relocation, IP3R is accompanied by other endoplasmic reticulum (ER) proteins: the Ca2+ pump sarcoendoplasmic reticulum calcium ATPase, the lumenal Ca2+-binding protein calreticulin, the ER lumen-addressed green fluorescent protein, and, to a lesser extent, the membrane chaperone calbindin. The specificity of these translocations was demonstrated by their inhibition by both a Shank1 fragment and the dominant-negative Homer1a. Activation in Shank1B-transfected neurons of the metabotropic glutamatergic receptors 1/5 (mGluRs1/5), which induce IP3 generation with ensuing Ca2+ release from the stores, triggered considerable increases in Ca2+-dependent responses: activation of the big K+ channel, which was revealed by patch clamping, and extracellular signal-regulated protein kinase (ERK) phosphorylation. The interaction of Shank1B and Homer1b appears as the molecular mechanism linking mGluRs1/5, strategically located in the spines, to IP3R with the integration of entire ER cisternas in the PSD and with consequences on both local Ca 2+ homeostasis and overall neuronal signaling.

AB - A key aspect of postsynaptic function, also important for plasticity, is the segregation within dendritic spines of Ca2+ rises attributable to release from intracellular stores. Previous studies have shown that overexpression in hippocampal neurons of two postsynaptic density (PSD) scaffold proteins, Shank1B and Homer1b, induces spine maturation, including translocation of the intracellular Ca2+ channel inositol trisphosphate receptor (IP3R). The structural and functional significance of these processes remained undefined. Here, we show that in its relocation, IP3R is accompanied by other endoplasmic reticulum (ER) proteins: the Ca2+ pump sarcoendoplasmic reticulum calcium ATPase, the lumenal Ca2+-binding protein calreticulin, the ER lumen-addressed green fluorescent protein, and, to a lesser extent, the membrane chaperone calbindin. The specificity of these translocations was demonstrated by their inhibition by both a Shank1 fragment and the dominant-negative Homer1a. Activation in Shank1B-transfected neurons of the metabotropic glutamatergic receptors 1/5 (mGluRs1/5), which induce IP3 generation with ensuing Ca2+ release from the stores, triggered considerable increases in Ca2+-dependent responses: activation of the big K+ channel, which was revealed by patch clamping, and extracellular signal-regulated protein kinase (ERK) phosphorylation. The interaction of Shank1B and Homer1b appears as the molecular mechanism linking mGluRs1/5, strategically located in the spines, to IP3R with the integration of entire ER cisternas in the PSD and with consequences on both local Ca 2+ homeostasis and overall neuronal signaling.

KW - Big K channel

KW - ER calcium stores

KW - ERK1/2

KW - Homer

KW - mGluR

KW - Postsynaptic density

KW - Shank

UR - http://www.scopus.com/inward/record.url?scp=18244374184&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=18244374184&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.4822-04.2005

DO - 10.1523/JNEUROSCI.4822-04.2005

M3 - Article

C2 - 15872106

AN - SCOPUS:18244374184

VL - 25

SP - 4587

EP - 4592

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 18

ER -