Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: β-amyloid-driven synaptic depression requires PDZ protein interaction at AMPA-receptor subunit GluA3 Soluble oligomeric amyloid-{beta} (A{beta}) is a prime suspect to cause cognitive deficits in Alzheimers disease and weakens synapses by removing AMPA-type glutamate receptors (AMPARs). We show that synapses of CA1 pyramidal neurons become vulnerable to A{beta} when they express AMPAR subunit GluA3. We found that A{beta}-oligomers reduce the levels of GluA3 immobilized at spines, indicating they deplete GluA3-containing AMPARs from synapses. These A{beta}-driven effects critically depended on the PDZ-binding motif of GluA3. When GluA3 was expressed with a single amino acid mutation in its PDZ-binding motif that prevents GRIP binding, it did not end up at spines and A{beta} failed to trigger synaptic depression. GluA3 with a different point mutation in the PDZ-motif that leaves GRIP-binding intact but prevents its endocytosis, was present at spines in normal amounts but was fully resistant to effects of A{beta}. Our data indicate that A{beta}-mediated synaptic depression requires the removal of GluA3 from synapses. We propose that GRIP-detachment from GluA3 is a critical early step in the cascade of events through which A{beta} accumulation causes a loss of synapse.
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The categories of this paper are: evolutionary
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The categories of this paper are: communication
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The categories of this paper are: developmental
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The categories of this paper are: biology
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The categories of this paper are: biophysics
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The categories of this paper are: genetics
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The categories of this paper are: plant
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The categories of this paper are: pathology
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The categories of this paper are: immunology
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The categories of this paper are: pharmacology
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The categories of this paper are: animal
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The categories of this paper are: cognition
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The categories of this paper are: genomics
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The categories of this paper are: ecology
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The categories of this paper are: epidemiology
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The categories of this paper are: biochemistry