Complex formation of APP with GABA(B) receptors links axonal trafficking to amyloidogenic processing

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F19%3A00508267" target="_blank" >RIV/68378041:_____/19:00508267 - isvavai.cz</a>

Result on the web

<a href="https://www.nature.com/articles/s41467-019-09164-3" target="_blank" >https://www.nature.com/articles/s41467-019-09164-3</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41467-019-09164-3" target="_blank" >10.1038/s41467-019-09164-3</a>

Result language

angličtina

Original language name

Complex formation of APP with GABA(B) receptors links axonal trafficking to amyloidogenic processing

Original language description

GABA(B) receptors (GBRs) are key regulators of synaptic release but little is known about trafficking mechanisms that control their presynaptic abundance. We now show that sequence-related epitopes in APP, AJAP-1 and PIANP bind with nanomolar affinities to the N-terminal sushi-domain of presynaptic GBRs. Of the three interacting proteins, selectively the genetic loss of APP impaired GBR-mediated presynaptic inhibition and axonal GBR expression. Proteomic and functional analyses revealed that APP associates with JIP and calsyntenin proteins that link the APP/GBR complex in cargo vesicles to the axonal trafficking motor. Complex formation with GBRs stabilizes APP at the cell surface and reduces proteolysis of APP to A beta, a component of senile plaques in Alzheimer's disease patients. Thus, APP/GBR complex formation links presynaptic GBR trafficking to A beta formation. Our findings support that dysfunctional axonal trafficking and reduced GBR expression in Alzheimer's disease increases A beta formation.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30103 - Neurosciences (including psychophysiology)

Project

<a href="/en/project/GA16-17823S" target="_blank" >GA16-17823S: The role of GABAB receptors in animal models of tinnitus</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Nature Communications

ISSN

2041-1723

e-ISSN

—

Volume of the periodical

10

Issue of the periodical within the volume

mar

Country of publishing house

GB - UNITED KINGDOM

Number of pages

17

Pages from-to

1331

UT code for WoS article

000461995800002

EID of the result in the Scopus database

2-s2.0-85063319718