Neuroligin 1 is dynamically exchanged at postsynaptic sites.
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Neuroligin 1 is dynamically exchanged at postsynaptic sites. / Schapitz, Inga; Behrend, Bardo; Pechmann, Yvonne; Lappe-Siefke, Corinna; Kneussel, Silas J; Wallace, Karen E; Stempel, A Vanessa; Buck, Friedrich; Grant, Seth G N; Schweizer, Michaela; Schmitz, Dietmar; Schwarz, Jürgen; Holzbaur, Erika L F; Kneussel, Matthias.
In: J NEUROSCI, Vol. 30, No. 38, 38, 2010, p. 12733-12744.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Neuroligin 1 is dynamically exchanged at postsynaptic sites.
AU - Schapitz, Inga
AU - Behrend, Bardo
AU - Pechmann, Yvonne
AU - Lappe-Siefke, Corinna
AU - Kneussel, Silas J
AU - Wallace, Karen E
AU - Stempel, A Vanessa
AU - Buck, Friedrich
AU - Grant, Seth G N
AU - Schweizer, Michaela
AU - Schmitz, Dietmar
AU - Schwarz, Jürgen
AU - Holzbaur, Erika L F
AU - Kneussel, Matthias
PY - 2010
Y1 - 2010
N2 - Neuroligins are postsynaptic cell adhesion molecules that associate with presynaptic neurexins. Both factors form a transsynaptic connection, mediate signaling across the synapse, specify synaptic functions, and play a role in synapse formation. Neuroligin dysfunction impairs synaptic transmission, disrupts neuronal networks, and is thought to participate in cognitive diseases. Here we report that chemical treatment designed to induce long-term potentiation or long-term depression (LTD) induces neuroligin 1/3 turnover, leading to either increased or decreased surface membrane protein levels, respectively. Despite its structural role at a crucial transsynaptic position, GFP-neuroligin 1 leaves synapses in hippocampal neurons over time with chemical LTD-induced neuroligin internalization depending on an intact microtubule cytoskeleton. Accordingly, neuroligin 1 and its binding partner postsynaptic density protein-95 (PSD-95) associate with components of the dynein motor complex and undergo retrograde cotransport with a dynein subunit. Transgenic depletion of dynein function in mice causes postsynaptic NLG1/3 and PSD-95 enrichment. In parallel, PSD lengths and spine head sizes are significantly increased, a phenotype similar to that observed upon transgenic overexpression of NLG1 (Dahlhaus et al., 2010). Moreover, application of a competitive PSD-95 peptide and neuroligin 1 C-terminal mutagenesis each specifically alter neuroligin 1 surface membrane expression and interfere with its internalization. Our data suggest the concept that synaptic plasticity regulates neuroligin turnover through active cytoskeleton transport.
AB - Neuroligins are postsynaptic cell adhesion molecules that associate with presynaptic neurexins. Both factors form a transsynaptic connection, mediate signaling across the synapse, specify synaptic functions, and play a role in synapse formation. Neuroligin dysfunction impairs synaptic transmission, disrupts neuronal networks, and is thought to participate in cognitive diseases. Here we report that chemical treatment designed to induce long-term potentiation or long-term depression (LTD) induces neuroligin 1/3 turnover, leading to either increased or decreased surface membrane protein levels, respectively. Despite its structural role at a crucial transsynaptic position, GFP-neuroligin 1 leaves synapses in hippocampal neurons over time with chemical LTD-induced neuroligin internalization depending on an intact microtubule cytoskeleton. Accordingly, neuroligin 1 and its binding partner postsynaptic density protein-95 (PSD-95) associate with components of the dynein motor complex and undergo retrograde cotransport with a dynein subunit. Transgenic depletion of dynein function in mice causes postsynaptic NLG1/3 and PSD-95 enrichment. In parallel, PSD lengths and spine head sizes are significantly increased, a phenotype similar to that observed upon transgenic overexpression of NLG1 (Dahlhaus et al., 2010). Moreover, application of a competitive PSD-95 peptide and neuroligin 1 C-terminal mutagenesis each specifically alter neuroligin 1 surface membrane expression and interfere with its internalization. Our data suggest the concept that synaptic plasticity regulates neuroligin turnover through active cytoskeleton transport.
M3 - SCORING: Zeitschriftenaufsatz
VL - 30
SP - 12733
EP - 12744
JO - J NEUROSCI
JF - J NEUROSCI
SN - 0270-6474
IS - 38
M1 - 38
ER -