Soluble Aβ1-42 increases the heterogeneity in synaptic vesicle pool size among synapses by suppressing intersynaptic vesicle sharing

Molecular Brain
Daehun Park, Sunghoe Chang

Abstract

Growing evidence has indicated that prefibrillar form of soluble amyloid beta (sAβ1-42) is the major causative factor in the synaptic dysfunction associated with AD. The molecular changes leading to presynaptic dysfunction caused by sAβ1-42, however, still remains elusive. Recently, we found that sAβ1-42 inhibits chemically induced long-term potentiation-induced synaptogenesis by suppressing the intersynaptic vesicle trafficking through calcium (Ca2+) dependent hyperphosphorylation of synapsin and CaMKIV. However, it is still unclear how sAβ1-42 increases intracellular Ca2+ that induces hyperphosphorylation of CaMKIV and synapsin, and what is the functional consequences of sAβ1-42-induced defects in intersynaptic vesicle trafficking in physiological conditions. In this study, we showed that sAβ1-42elevated intracellular Ca2+ through not only extracellular Ca2+ influx but also Ca2+ release from mitochondria. Surprisingly, without Ca2+ release from mitochondria, sAβ1-42 failed to increase intracellular Ca2+ even in the presence of normal extracellular Ca2+. We further found that sAβ1-42-induced mitochondria Ca2+ release alone sufficiently increased Serine 9 phosphorylation of synapsin. By blocking synaptic vesicle reallocation, s...Continue Reading

References

Jan 1, 1988·Advances in Experimental Medicine and Biology·T E GunterK K Gunter
Jan 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·N ArispeH B Pollard
Feb 20, 1996·Proceedings of the National Academy of Sciences of the United States of America·N ArispeE Rojas
Sep 2, 1997·Proceedings of the National Academy of Sciences of the United States of America·Y LuoV M Ingram
Oct 24, 2001·The Journal of Biological Chemistry·Y I DeryabinaR A Zvyagilskaya
Jun 12, 2002·The Journal of Biological Chemistry·Karie N DahlgrenMary Jo LaDu
Oct 26, 2002·Science·Dennis J Selkoe
Feb 8, 2006·Nature Neuroscience·Kevin J DarcyYukiko Goda
Jul 14, 2006·Neurobiology of Aging·Arlene M ManelliMary Jo LaDu
Jan 25, 2007·Nature Reviews. Molecular Cell Biology·Christian Haass, Dennis J Selkoe
Mar 16, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ganesh M ShankarBernardo L Sabatini
Mar 21, 2007·Molecular and Cellular Neurosciences·Barbara CalabreseShelley Halpain
Jan 25, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Volker NimmrichClaus Bruehl
Apr 9, 2008·Nature Neuroscience·Diego E BermanGilbert Di Paolo
Aug 1, 2008·Neuron·Kim N Green, Frank M LaFerla
Jan 2, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Daniela PuzzoOttavio Arancio
Mar 24, 2009·Proceedings of the National Academy of Sciences of the United States of America·Herman MorenoRodolfo R Llinás
Oct 27, 2009·Biochimica Et Biophysica Acta·Paula I MoreiraGeorge Perry
Mar 10, 2010·The Journal of Biological Chemistry·Angelo DemuroGrace E Stutzmann
Mar 30, 2010·Journal of Neurochemistry·Ana Gabriela HenriquesOdete A B da Cruz E Silva
Oct 20, 2010·Proceedings of the National Academy of Sciences of the United States of America·Peer HoopmannSilvio O Rizzoli
Jan 19, 2011·Biochimica Et Biophysica Acta·Marcus J Calkins, P Hemachandra Reddy
Jul 9, 2011·Pharmacological Reviews·Grace E Stutzmann, Mark P Mattson
Jan 31, 2012·Nature Neuroscience·Iryna BenilovaBart De Strooper
Mar 24, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ayelet OrenbuchDaniel Gitler
Jun 12, 2013·The Journal of Physiology·Michael J Berridge
Jun 26, 2015·The EMBO Journal·Jerome Di Giovanni, Zu-Hang Sheng
Oct 4, 2016·Trends in Biochemical Sciences·Anna RaffaelloRosario Rizzuto

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Citations

Sep 29, 2019·Journal of Alzheimer's Disease : JAD·Francesca FagianiStefano Govoni
Aug 28, 2020·Science Advances·Bradlee L HeckmannDouglas R Green
Jun 22, 2018·Neural Regeneration Research·Chommanad Lerdkrai, Olga Garaschuk

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Methods Mentioned

BETA
fluorescence recovery after photobleaching
transfection

Software Mentioned

Origin
SPSS
MetaMorph
OriginPro
ImageJ
Olympus Fluoview

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