PMID- 26296617
OWN - NLM
STAT- MEDLINE
DCOM- 20160210
LR  - 20220310
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Linking)
VI  - 135
IP  - 3
DP  - 2015 Nov
TI  - ADAM10 and BACE1 are localized to synaptic vesicles.
PG  - 606-15
LID - 10.1111/jnc.13287 [doi]
AB  - Synaptic degeneration and accumulation of the neurotoxic amyloid beta-peptide (Abeta) 
      in the brain are hallmarks of Alzheimer disease. Abeta is produced by sequential 
      cleavage of the amyloid precursor protein (APP), by the beta-secretase beta-site APP 
      cleaving enzyme 1 (BACE1) and gamma-secretase. However, Abeta generation is precluded if 
      APP is cleaved by the alpha-secretase ADAM10 instead of BACE1. We have previously 
      shown that Abeta can be produced locally at the synapse. To study the synaptic 
      localization of the APP processing enzymes we used western blotting to 
      demonstrate that, compared to total brain homogenate, ADAM10 and BACE1 were 
      greatly enriched in synaptic vesicles isolated from rat brain using 
      controlled-pore glass chromatography, whereas Presenilin1 was the only enriched 
      component of the gamma-secretase complex. Moreover, we detected ADAM10 activity in 
      synaptic vesicles and enrichment of the intermediate APP-C-terminal fragments 
      (APP-CTFs). We confirmed the western blotting findings using in situ proximity 
      ligation assay to demonstrate close proximity of ADAM10 and BACE1 with the 
      synaptic vesicle marker synaptophysin in intact mouse primary hippocampal 
      neurons. In contrast, only sparse co-localization of active gamma-secretase and 
      synaptophysin was detected. These results indicate that the first step of APP 
      processing occurs in synaptic vesicles whereas the final step is more likely to 
      take place elsewhere.
CI  - (c) 2015 International Society for Neurochemistry.
FAU - Lundgren, Jolanta L
AU  - Lundgren JL
AUID- ORCID: 0000-0003-2440-4686
AD  - Karolinska Institutet, Department of Neurobiology, Care Science and Society, 
      Division of Neurogeriatrics, Center for Alzheimer Research, Huddinge, Sweden.
FAU - Ahmed, Saheeb
AU  - Ahmed S
AD  - European Neuroscience Institute, Gottingen, Germany.
FAU - Schedin-Weiss, Sophia
AU  - Schedin-Weiss S
AD  - Karolinska Institutet, Department of Neurobiology, Care Science and Society, 
      Division of Neurogeriatrics, Center for Alzheimer Research, Huddinge, Sweden.
FAU - Gouras, Gunnar K
AU  - Gouras GK
AD  - Lund University, Department of Experimental Medical Science, Experimental 
      Dementia Research Unit, Lund, Sweden.
FAU - Winblad, Bengt
AU  - Winblad B
AD  - Karolinska Institutet, Department of Neurobiology, Care Science and Society, 
      Division of Neurogeriatrics, Center for Alzheimer Research, Huddinge, Sweden.
FAU - Tjernberg, Lars O
AU  - Tjernberg LO
AD  - Karolinska Institutet, Department of Neurobiology, Care Science and Society, 
      Division of Neurogeriatrics, Center for Alzheimer Research, Huddinge, Sweden.
FAU - Frykman, Susanne
AU  - Frykman S
AD  - Karolinska Institutet, Department of Neurobiology, Care Science and Society, 
      Division of Neurogeriatrics, Center for Alzheimer Research, Huddinge, Sweden.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150917
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Membrane Proteins)
RN  - EC 3.4.- (Amyloid Precursor Protein Secretases)
RN  - EC 3.4.23.- (Aspartic Acid Endopeptidases)
RN  - EC 3.4.23.46 (Bace1 protein, mouse)
RN  - EC 3.4.24.- (ADAM Proteins)
RN  - EC 3.4.24.81 (ADAM10 Protein)
RN  - EC 3.4.24.81 (Adam10 protein, mouse)
SB  - IM
MH  - ADAM Proteins/*analysis
MH  - ADAM10 Protein
MH  - Amyloid Precursor Protein Secretases/*analysis
MH  - Animals
MH  - Aspartic Acid Endopeptidases/*analysis
MH  - Cells, Cultured
MH  - Hippocampus/chemistry/cytology
MH  - Membrane Proteins/*analysis
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Rats
MH  - Synaptic Vesicles/*chemistry
OTO - NOTNLM
OT  - APP processing
OT  - Alzheimer Disease
OT  - nerve terminals
OT  - secretases
OT  - synapse
OT  - trafficking
EDAT- 2015/08/25 06:00
MHDA- 2016/02/11 06:00
CRDT- 2015/08/23 06:00
PHST- 2015/04/13 00:00 [received]
PHST- 2015/06/26 00:00 [revised]
PHST- 2015/07/28 00:00 [accepted]
PHST- 2015/08/23 06:00 [entrez]
PHST- 2015/08/25 06:00 [pubmed]
PHST- 2016/02/11 06:00 [medline]
AID - 10.1111/jnc.13287 [doi]
PST - ppublish
SO  - J Neurochem. 2015 Nov;135(3):606-15. doi: 10.1111/jnc.13287. Epub 2015 Sep 17.