NCAM/spectrin complex disassembly results in PSD perforation and postsynaptic endocytic zone formation.
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NCAM/spectrin complex disassembly results in PSD perforation and postsynaptic endocytic zone formation. / Puchkov, Dmytro; Leshchyns´ka, Iryna; Nikonenko, Alexander; Schachner, Melitta; Sytnyk, Vladimir.
in: CEREB CORTEX, Jahrgang 21, Nr. 10, 10, 2011, S. 2217-2232.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - NCAM/spectrin complex disassembly results in PSD perforation and postsynaptic endocytic zone formation.
AU - Puchkov, Dmytro
AU - Leshchyns´ka, Iryna
AU - Nikonenko, Alexander
AU - Schachner, Melitta
AU - Sytnyk, Vladimir
PY - 2011
Y1 - 2011
N2 - Mechanisms inducing perforation of the postsynaptic density (PSD) are poorly understood. We show that neural cell adhesion molecule- deficient (NCAM-/-) hippocampal neurons have an abnormally high percentage of synapses with perforated PSDs. The percentage of synapses with perforated PSDs is also increased in wild-type (NCAM+/+) neurons after the disruption of the NCAM/spectrin complex indicating that the NCAM-assembled spectrin cytoskeleton maintains the structural integrity of PSDs. We demonstrate that PSD perforations contain endocytic zones involved in ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) internalization. Induction of long-term potentiation in NCAM+/+ neurons accompanied by insertion of AMPAR into the neuronal cell surface is subsequently followed by formation of perforated synapses and AMPAR endocytosis suggesting that perforation of PSDs is important for membrane homeostasis in activated synapses. In NCAM-/- or NCAM+/+ neurons with dissociated spectrin meshwork, AMPAR endocytosis is enhanced under conditions of basal activity. An abnormally high rate of postsynaptic membrane endocytosis may thus contribute to brain pathologies associated with mutations in NCAM or spectrin.
AB - Mechanisms inducing perforation of the postsynaptic density (PSD) are poorly understood. We show that neural cell adhesion molecule- deficient (NCAM-/-) hippocampal neurons have an abnormally high percentage of synapses with perforated PSDs. The percentage of synapses with perforated PSDs is also increased in wild-type (NCAM+/+) neurons after the disruption of the NCAM/spectrin complex indicating that the NCAM-assembled spectrin cytoskeleton maintains the structural integrity of PSDs. We demonstrate that PSD perforations contain endocytic zones involved in ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) internalization. Induction of long-term potentiation in NCAM+/+ neurons accompanied by insertion of AMPAR into the neuronal cell surface is subsequently followed by formation of perforated synapses and AMPAR endocytosis suggesting that perforation of PSDs is important for membrane homeostasis in activated synapses. In NCAM-/- or NCAM+/+ neurons with dissociated spectrin meshwork, AMPAR endocytosis is enhanced under conditions of basal activity. An abnormally high rate of postsynaptic membrane endocytosis may thus contribute to brain pathologies associated with mutations in NCAM or spectrin.
M3 - SCORING: Journal article
VL - 21
SP - 2217
EP - 2232
JO - CEREB CORTEX
JF - CEREB CORTEX
SN - 1047-3211
IS - 10
M1 - 10
ER -
