Dramatic depletion of cell surface m2 muscarinic receptor due to limited delivery from intracytoplasmic stores in neurons of acetylcholinesterase-deficient mice

Véronique Bernard, Corinne Brana, Isabel Liste, Oksana Lockridge, Bertrand Bloch

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41 Citations (Scopus)

Abstract

We have studied the consequences of the constitutive acetylcholinesterase (AChE) deficiency in knockout mice for the AChE gene on the subcellular localization of the m2 receptor (m2R) and the regulation of its intraneuronal compartmentalization by the cholinergic environment, using immunohistochemistry at light and electron microscopic levels. (1) In AChE +/+ mice in vivo, m2R is mainly located at the neuronal membrane in striatum, hippocampus, and cortex. In AChE -/- mice, m2R is almost absent at the membrane but is accumulated in the endoplasmic reticulum and Golgi complex. (2) In vivo and in vitro (organotypic culture) dynamic studies demonstrate that the balance between membrane and intracytoplasmic m2R can be regulated by the cholinergic influence: In AChE -/- mice, m2R is translocated from the cytoplasm to the cell surface after (1) blockade of muscarinic receptors by atropine, (2) supplementation of AChE -/- neurons with AChE in vitro, and (3) disruption of the cortical and hippocampal cholinergic afferents in vitro. Our results suggest that the neurochemical environment may contribute to the control of the abundance and availability of cell surface receptors, and consequently to the control of neuronal sensitivity to neurotransmitters or drugs, by regulating their delivery from the endoplasmic reticulum and Golgi complex.

Original languageEnglish (US)
Pages (from-to)121-133
Number of pages13
JournalMolecular and Cellular Neuroscience
Volume23
Issue number1
DOIs
StatePublished - May 1 2003

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Muscarinic M2 Receptors
Acetylcholinesterase
Neurons
Cholinergic Agents
Golgi Apparatus
Endoplasmic Reticulum
Membranes
Cell Surface Receptors
Muscarinic Receptors
Atropine
Knockout Mice
Neurotransmitter Agents
Hippocampus
Cytoplasm
Immunohistochemistry
Electrons
Light

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Dramatic depletion of cell surface m2 muscarinic receptor due to limited delivery from intracytoplasmic stores in neurons of acetylcholinesterase-deficient mice. / Bernard, Véronique; Brana, Corinne; Liste, Isabel; Lockridge, Oksana; Bloch, Bertrand.

In: Molecular and Cellular Neuroscience, Vol. 23, No. 1, 01.05.2003, p. 121-133.

Research output: Contribution to journalArticle

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