TY - JOUR
T1 - Sorting Nexin 27 regulates basal and activity-dependent trafficking of AMPARs
AU - Hussain, Natasha
AU - Diering, Graham H.
AU - Sole, Jonathan
AU - Anggono, Victor
AU - Huganir, Richard L.
PY - 2014/8/12
Y1 - 2014/8/12
N2 - Activity-dependent changes in synaptic strength have long been postulated as cellular correlates of learning and memory. Long-term potentiation (LTP), a well characterized form of synaptic plasticity, is often expressed as an increase in the number of postsynaptic AMPAtype glutamate receptors (AMPARs). Although the precise molecular mechanisms governing LTP remain elusive, this study identifies one member of the sorting nexin family, Sorting Nexin 27 (SNX27), as a critical component in this process. The ability of sorting nexins to bind specific phospholipids as well as their propensity to form protein- protein complexes, points to a role for these proteins in membrane trafficking and protein sorting. Here, we demonstrate that SNX27 binds to AMPARs, and that this interaction is regulated in an activity-dependent manner. Furthermore, we provide evidence that SNX27 is synaptically enriched and its level of expression regulates targeting of AMPARs to the neuronal surface. Loss of SNX27 abolishes recruitment of surface AMPARs during chemical LTP. Collectively, our data suggest a role for SNX27 in modulating synaptic plasticity through regulated interaction with AMPARs.
AB - Activity-dependent changes in synaptic strength have long been postulated as cellular correlates of learning and memory. Long-term potentiation (LTP), a well characterized form of synaptic plasticity, is often expressed as an increase in the number of postsynaptic AMPAtype glutamate receptors (AMPARs). Although the precise molecular mechanisms governing LTP remain elusive, this study identifies one member of the sorting nexin family, Sorting Nexin 27 (SNX27), as a critical component in this process. The ability of sorting nexins to bind specific phospholipids as well as their propensity to form protein- protein complexes, points to a role for these proteins in membrane trafficking and protein sorting. Here, we demonstrate that SNX27 binds to AMPARs, and that this interaction is regulated in an activity-dependent manner. Furthermore, we provide evidence that SNX27 is synaptically enriched and its level of expression regulates targeting of AMPARs to the neuronal surface. Loss of SNX27 abolishes recruitment of surface AMPARs during chemical LTP. Collectively, our data suggest a role for SNX27 in modulating synaptic plasticity through regulated interaction with AMPARs.
KW - PDZ-domain
KW - PX domain
KW - Postsynaptic density
KW - Proteomics
UR - http://www.scopus.com/inward/record.url?scp=84905993620&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84905993620&partnerID=8YFLogxK
U2 - 10.1073/pnas.1412415111
DO - 10.1073/pnas.1412415111
M3 - Article
C2 - 25071192
AN - SCOPUS:84905993620
SN - 0027-8424
VL - 111
SP - 11840
EP - 11845
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 32
ER -