Dramatic depletion of cell surface m2 muscarinic receptor due to limited delivery from intracytoplasmic stores in neurons of acetylcholinesterase-deficient mice.
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.
Bernard
Véronique
V
Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5541, Laboratoire d'Histologie-Embryologie, Université Victor Ségalen-Bordeaux 2, 146 rue Léo-Saignat, France. Veronique.Bernard@umr5541.u-bordeaux2.fr
Brana
Corinne
C
Liste
Isabel
I
Lockridge
Oksana
O
Bloch
Bertrand
B
D000110:Acetylcholinesterase / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D002799:Cholinergic Fibers / Q000378:metabolism; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D009924:Organ Culture Techniques; D043585:Receptor, Muscarinic M2; D011956:Receptors, Cell Surface / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism*
D018727:Muscarinic Antagonists; D043585:Receptor, Muscarinic M2; D011956:Receptors, Cell Surface; D011976:Receptors, Muscarinic; D001285:Atropine; D000110:Acetylcholinesterase