Control of Neuronal Ryanodine Receptor-Mediated Calcium Signaling by Calsenilin

Michael A. Grillo, Stephanie Grillo, Bryan C. Gerdes, Jacob G. Kraus, Peter Koulen

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Calsenilin is a calcium ion (Ca 2+ )-binding protein involved in regulating the intracellular concentration of Ca 2+ , a second messenger that controls multiple cellular signaling pathways. The ryanodine receptor (RyR) amplifies Ca 2+ signals entering the cytoplasm by releasing Ca 2+ from endoplasmic reticulum (ER) stores, a process termed calcium-induced calcium release (CICR). Here, we describe a novel mechanism, in which calsenilin controls the activity of neuronal RyRs. We show calsenilin co-localized with RyR2 and 3 in the ER of mouse hippocampal and cortical neurons using immunocytochemistry. The underlying protein-protein interaction between calsenilin and the RyR was determined in mouse central nervous system (CNS) neurons using immunoprecipitation studies. The functional relevance of this interaction was assayed with single-channel electrophysiology. At low physiological Ca 2+ concentrations, calsenilin binding to the cytoplasmic face of neuronal RyRs decreased the RyR’s open probability, while calsenilin increased the open probability at high physiological Ca 2+ concentrations. This novel molecular mechanism was studied further at the cellular level, where faster release kinetics of caffeine-induced Ca 2+ release were measured in SH-SY5Y neuroblastoma cells overexpressing calsenilin. The interaction between calsenilin and neuronal RyRs reveals a new regulatory mechanism and possibly a novel pharmacological target for the control of Ca 2+ release from intracellular stores.

Original languageEnglish (US)
Pages (from-to)525-534
Number of pages10
JournalMolecular Neurobiology
Volume56
Issue number1
DOIs
StatePublished - Jan 1 2019

Fingerprint

Kv Channel-Interacting Proteins
Ryanodine Receptor Calcium Release Channel
Calcium Signaling
Calcium
Endoplasmic Reticulum
Neurons
Electrophysiology
Second Messenger Systems
Caffeine
Neuroblastoma
Immunoprecipitation
Cytoplasm
Proteins
Central Nervous System
Immunohistochemistry
Pharmacology
Ions

All Science Journal Classification (ASJC) codes

  • Neuroscience (miscellaneous)
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Grillo, Michael A. ; Grillo, Stephanie ; Gerdes, Bryan C. ; Kraus, Jacob G. ; Koulen, Peter. / Control of Neuronal Ryanodine Receptor-Mediated Calcium Signaling by Calsenilin. In: Molecular Neurobiology. 2019 ; Vol. 56, No. 1. pp. 525-534.
@article{6f14c3e8099a4892aae4b64e373e368f,
title = "Control of Neuronal Ryanodine Receptor-Mediated Calcium Signaling by Calsenilin",
abstract = "Calsenilin is a calcium ion (Ca 2+ )-binding protein involved in regulating the intracellular concentration of Ca 2+ , a second messenger that controls multiple cellular signaling pathways. The ryanodine receptor (RyR) amplifies Ca 2+ signals entering the cytoplasm by releasing Ca 2+ from endoplasmic reticulum (ER) stores, a process termed calcium-induced calcium release (CICR). Here, we describe a novel mechanism, in which calsenilin controls the activity of neuronal RyRs. We show calsenilin co-localized with RyR2 and 3 in the ER of mouse hippocampal and cortical neurons using immunocytochemistry. The underlying protein-protein interaction between calsenilin and the RyR was determined in mouse central nervous system (CNS) neurons using immunoprecipitation studies. The functional relevance of this interaction was assayed with single-channel electrophysiology. At low physiological Ca 2+ concentrations, calsenilin binding to the cytoplasmic face of neuronal RyRs decreased the RyR’s open probability, while calsenilin increased the open probability at high physiological Ca 2+ concentrations. This novel molecular mechanism was studied further at the cellular level, where faster release kinetics of caffeine-induced Ca 2+ release were measured in SH-SY5Y neuroblastoma cells overexpressing calsenilin. The interaction between calsenilin and neuronal RyRs reveals a new regulatory mechanism and possibly a novel pharmacological target for the control of Ca 2+ release from intracellular stores.",
author = "Grillo, {Michael A.} and Stephanie Grillo and Gerdes, {Bryan C.} and Kraus, {Jacob G.} and Peter Koulen",
year = "2019",
month = "1",
day = "1",
doi = "10.1007/s12035-018-1080-2",
language = "English (US)",
volume = "56",
pages = "525--534",
journal = "Molecular Neurobiology",
issn = "0893-7648",
publisher = "Humana Press",
number = "1",

}

Control of Neuronal Ryanodine Receptor-Mediated Calcium Signaling by Calsenilin. / Grillo, Michael A.; Grillo, Stephanie; Gerdes, Bryan C.; Kraus, Jacob G.; Koulen, Peter.

In: Molecular Neurobiology, Vol. 56, No. 1, 01.01.2019, p. 525-534.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Control of Neuronal Ryanodine Receptor-Mediated Calcium Signaling by Calsenilin

AU - Grillo, Michael A.

AU - Grillo, Stephanie

AU - Gerdes, Bryan C.

AU - Kraus, Jacob G.

AU - Koulen, Peter

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Calsenilin is a calcium ion (Ca 2+ )-binding protein involved in regulating the intracellular concentration of Ca 2+ , a second messenger that controls multiple cellular signaling pathways. The ryanodine receptor (RyR) amplifies Ca 2+ signals entering the cytoplasm by releasing Ca 2+ from endoplasmic reticulum (ER) stores, a process termed calcium-induced calcium release (CICR). Here, we describe a novel mechanism, in which calsenilin controls the activity of neuronal RyRs. We show calsenilin co-localized with RyR2 and 3 in the ER of mouse hippocampal and cortical neurons using immunocytochemistry. The underlying protein-protein interaction between calsenilin and the RyR was determined in mouse central nervous system (CNS) neurons using immunoprecipitation studies. The functional relevance of this interaction was assayed with single-channel electrophysiology. At low physiological Ca 2+ concentrations, calsenilin binding to the cytoplasmic face of neuronal RyRs decreased the RyR’s open probability, while calsenilin increased the open probability at high physiological Ca 2+ concentrations. This novel molecular mechanism was studied further at the cellular level, where faster release kinetics of caffeine-induced Ca 2+ release were measured in SH-SY5Y neuroblastoma cells overexpressing calsenilin. The interaction between calsenilin and neuronal RyRs reveals a new regulatory mechanism and possibly a novel pharmacological target for the control of Ca 2+ release from intracellular stores.

AB - Calsenilin is a calcium ion (Ca 2+ )-binding protein involved in regulating the intracellular concentration of Ca 2+ , a second messenger that controls multiple cellular signaling pathways. The ryanodine receptor (RyR) amplifies Ca 2+ signals entering the cytoplasm by releasing Ca 2+ from endoplasmic reticulum (ER) stores, a process termed calcium-induced calcium release (CICR). Here, we describe a novel mechanism, in which calsenilin controls the activity of neuronal RyRs. We show calsenilin co-localized with RyR2 and 3 in the ER of mouse hippocampal and cortical neurons using immunocytochemistry. The underlying protein-protein interaction between calsenilin and the RyR was determined in mouse central nervous system (CNS) neurons using immunoprecipitation studies. The functional relevance of this interaction was assayed with single-channel electrophysiology. At low physiological Ca 2+ concentrations, calsenilin binding to the cytoplasmic face of neuronal RyRs decreased the RyR’s open probability, while calsenilin increased the open probability at high physiological Ca 2+ concentrations. This novel molecular mechanism was studied further at the cellular level, where faster release kinetics of caffeine-induced Ca 2+ release were measured in SH-SY5Y neuroblastoma cells overexpressing calsenilin. The interaction between calsenilin and neuronal RyRs reveals a new regulatory mechanism and possibly a novel pharmacological target for the control of Ca 2+ release from intracellular stores.

UR - http://www.scopus.com/inward/record.url?scp=85046413599&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85046413599&partnerID=8YFLogxK

U2 - 10.1007/s12035-018-1080-2

DO - 10.1007/s12035-018-1080-2

M3 - Article

VL - 56

SP - 525

EP - 534

JO - Molecular Neurobiology

JF - Molecular Neurobiology

SN - 0893-7648

IS - 1

ER -