The neural cell adhesion molecule promotes maturation of the presynaptic endocytotic machinery by switching synaptic vesicle recycling from adaptor protein 3 (AP-3)- to AP-2-dependent mechanisms
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The neural cell adhesion molecule promotes maturation of the presynaptic endocytotic machinery by switching synaptic vesicle recycling from adaptor protein 3 (AP-3)- to AP-2-dependent mechanisms. / Shetty, Aparna; Sytnyk, Vladimir; Leshchyns´ka, Iryna; Puchkov, Dmytro; Haucke, Volker; Schachner, Melitta.
in: J NEUROSCI, Jahrgang 33, Nr. 42, 16.10.2013, S. 16828-45.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - The neural cell adhesion molecule promotes maturation of the presynaptic endocytotic machinery by switching synaptic vesicle recycling from adaptor protein 3 (AP-3)- to AP-2-dependent mechanisms
AU - Shetty, Aparna
AU - Sytnyk, Vladimir
AU - Leshchyns´ka, Iryna
AU - Puchkov, Dmytro
AU - Haucke, Volker
AU - Schachner, Melitta
PY - 2013/10/16
Y1 - 2013/10/16
N2 - Newly formed synapses undergo maturation during ontogenetic development via mechanisms that remain poorly understood. We show that maturation of the presynaptic endocytotic machinery in CNS neurons requires substitution of the adaptor protein 3 (AP-3) with AP-2 at the presynaptic plasma membrane. In mature synapses, AP-2 associates with the intracellular domain of the neural cell adhesion molecule (NCAM). NCAM promotes binding of AP-2 over binding of AP-3 to presynaptic membranes, thus favoring the substitution of AP-3 for AP-2 during formation of mature synapses. The presynaptic endocytotic machinery remains immature in adult NCAM-deficient (NCAM-/-) mice accumulating AP-3 instead of AP-2 and its partner protein AP180 in synaptic membranes and vesicles. NCAM deficiency or disruption of the NCAM/AP-2 complex in wild-type (NCAM+/+) neurons by overexpression of AP-2 binding-defective mutant NCAM interferes with efficient retrieval of the synaptic vesicle v-SNARE synaptobrevin 2. Abnormalities in synaptic vesicle endocytosis and recycling may thus contribute to neurological disorders associated with mutations in NCAM.
AB - Newly formed synapses undergo maturation during ontogenetic development via mechanisms that remain poorly understood. We show that maturation of the presynaptic endocytotic machinery in CNS neurons requires substitution of the adaptor protein 3 (AP-3) with AP-2 at the presynaptic plasma membrane. In mature synapses, AP-2 associates with the intracellular domain of the neural cell adhesion molecule (NCAM). NCAM promotes binding of AP-2 over binding of AP-3 to presynaptic membranes, thus favoring the substitution of AP-3 for AP-2 during formation of mature synapses. The presynaptic endocytotic machinery remains immature in adult NCAM-deficient (NCAM-/-) mice accumulating AP-3 instead of AP-2 and its partner protein AP180 in synaptic membranes and vesicles. NCAM deficiency or disruption of the NCAM/AP-2 complex in wild-type (NCAM+/+) neurons by overexpression of AP-2 binding-defective mutant NCAM interferes with efficient retrieval of the synaptic vesicle v-SNARE synaptobrevin 2. Abnormalities in synaptic vesicle endocytosis and recycling may thus contribute to neurological disorders associated with mutations in NCAM.
KW - Adaptor Protein Complex 2
KW - Adaptor Protein Complex 3
KW - Animals
KW - CHO Cells
KW - Cricetulus
KW - Endocytosis
KW - HEK293 Cells
KW - Hippocampus
KW - Humans
KW - Mice
KW - Mice, Knockout
KW - Neural Cell Adhesion Molecules
KW - Neurons
KW - Presynaptic Terminals
KW - Synaptic Membranes
KW - Synaptic Vesicles
KW - Vesicle-Associated Membrane Protein 2
U2 - 10.1523/JNEUROSCI.2192-13.2013
DO - 10.1523/JNEUROSCI.2192-13.2013
M3 - SCORING: Journal article
C2 - 24133283
VL - 33
SP - 16828
EP - 16845
JO - J NEUROSCI
JF - J NEUROSCI
SN - 0270-6474
IS - 42
ER -
