SAP97-mediated ADAM10 trafficking from Golgi outposts depends on PKC phosphorylation

C. Saraceno, E. Marcello, D. Di Marino, B. Borroni, S. Claeysen, J. Perroy, A. Padovani, A. Tramontano, F. Gardoni, M. Di Luca

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

A disintegrin and metalloproteinase 10 (ADAM10) is the major α-secretase that catalyzes the amyloid precursor protein (APP) ectodomain shedding in the brain and prevents amyloid formation. Its activity depends on correct intracellular trafficking and on synaptic membrane insertion. Here, we describe that in hippocampal neurons the synapse-associated protein-97 (SAP97), an excitatory synapse scaffolding element, governs ADAM10 trafficking from dendritic Golgi outposts to synaptic membranes. This process is mediated by a previously uncharacterized protein kinase C phosphosite in SAP97 SRC homology 3 domain that modulates SAP97 association with ADAM10. Such mechanism is essential for ADAM10 trafficking from the Golgi outposts to the synapse, but does not affect ADAM10 transport from the endoplasmic reticulum. Notably, this process is altered in Alzheimer's disease brains. These results help in understanding the mechanism responsible for the modulation of ADAM10 intracellular path, and can constitute an innovative therapeutic strategy to finely tune ADAM10 shedding activity towards APP.

Original languageEnglish
Article numbere1547
JournalCell Death and Disease
Volume5
Issue number11
DOIs
Publication statusPublished - Jan 1 2014

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Disintegrins
Metalloproteases
Phosphorylation
Synaptic Membranes
Synapses
Amyloid Precursor Protein Secretases
Amyloid beta-Protein Precursor
Brain
human DLG1 protein
Amyloid
Endoplasmic Reticulum
Protein Kinase C
Alzheimer Disease
Neurons

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

Cite this

Saraceno, C., Marcello, E., Di Marino, D., Borroni, B., Claeysen, S., Perroy, J., ... Di Luca, M. (2014). SAP97-mediated ADAM10 trafficking from Golgi outposts depends on PKC phosphorylation. Cell Death and Disease, 5(11), [e1547]. https://doi.org/10.1038/cddis.2014.492

SAP97-mediated ADAM10 trafficking from Golgi outposts depends on PKC phosphorylation. / Saraceno, C.; Marcello, E.; Di Marino, D.; Borroni, B.; Claeysen, S.; Perroy, J.; Padovani, A.; Tramontano, A.; Gardoni, F.; Di Luca, M.

In: Cell Death and Disease, Vol. 5, No. 11, e1547, 01.01.2014.

Research output: Contribution to journalArticle

Saraceno, C, Marcello, E, Di Marino, D, Borroni, B, Claeysen, S, Perroy, J, Padovani, A, Tramontano, A, Gardoni, F & Di Luca, M 2014, 'SAP97-mediated ADAM10 trafficking from Golgi outposts depends on PKC phosphorylation', Cell Death and Disease, vol. 5, no. 11, e1547. https://doi.org/10.1038/cddis.2014.492
Saraceno, C. ; Marcello, E. ; Di Marino, D. ; Borroni, B. ; Claeysen, S. ; Perroy, J. ; Padovani, A. ; Tramontano, A. ; Gardoni, F. ; Di Luca, M. / SAP97-mediated ADAM10 trafficking from Golgi outposts depends on PKC phosphorylation. In: Cell Death and Disease. 2014 ; Vol. 5, No. 11.
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