APP and APLP2 interact with the synaptic release machinery and facilitate transmitter release at hippocampal synapses

Tomas Fanutza, Dolores del Prete, Michael J. Ford, Pablo E. Castillo, Luciano D’Adamio

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The amyloid precursor protein (APP), whose mutations cause familial Alzheimer’s disease, interacts with the synaptic release machinery, suggesting a role in neurotransmission. Here we mapped this interaction to the NH2-terminal region of the APP intracellular domain. A peptide encompassing this binding domain -named JCasp- is naturally produced by a γ-secretase/caspase double-cut of APP. JCasp interferes with the APP-presynaptic proteins interaction and, if linked to a cell-penetrating peptide, reduces glutamate release in acute hippocampal slices from wild-type but not APP deficient mice, indicating that JCasp inhibits APP function.The APP-like protein-2 (APLP2) also binds the synaptic release machinery. Deletion of APP and APLP2 produces synaptic deficits similar to those caused by JCasp. Our data support the notion that APP and APLP2 facilitate transmitter release, likely through the interaction with the neurotransmitter release machinery. Given the link of APP to Alzheimer’s disease, alterations of this synaptic role of APP could contribute to dementia.

Original languageEnglish (US)
Article numbere09743
JournaleLife
Volume4
Issue numberNOVEMBER2015
DOIs
StatePublished - Nov 9 2015

Fingerprint

Amyloid beta-Protein Precursor
Synapses
Machinery
Transmitters
Proteins
Alzheimer Disease
Cell-Penetrating Peptides
Amyloid Precursor Protein Secretases
Caspases
Amyloid
Synaptic Transmission
Neurotransmitter Agents
Dementia
Glutamic Acid
Peptides
Mutation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)
  • Neuroscience(all)

Cite this

APP and APLP2 interact with the synaptic release machinery and facilitate transmitter release at hippocampal synapses. / Fanutza, Tomas; del Prete, Dolores; Ford, Michael J.; Castillo, Pablo E.; D’Adamio, Luciano.

In: eLife, Vol. 4, No. NOVEMBER2015, e09743, 09.11.2015.

Research output: Contribution to journalArticle

Fanutza, Tomas ; del Prete, Dolores ; Ford, Michael J. ; Castillo, Pablo E. ; D’Adamio, Luciano. / APP and APLP2 interact with the synaptic release machinery and facilitate transmitter release at hippocampal synapses. In: eLife. 2015 ; Vol. 4, No. NOVEMBER2015.
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