A role for sorting nexin 27 in AMPA receptor trafficking.
Sorting nexin 27 (SNX27), a PDZ domain-containing endosomal protein, was recently shown to modulate glutamate receptor recycling in Down's syndrome. However, the precise molecular role of SNX27 in GluA1 trafficking is unclear. Here we report that SNX27 is enriched in dendrites and spines, along with recycling endosomes. Significantly, the mobilization of SNX27 along with recycling endosomes into spines was observed. Mechanistically, SNX27 interacts with K-ras GTPase via the RA domain; and following chemical LTP stimuli, K-ras is recruited to SNX27-enriched endosomes through a Ca(2+)/CaM-dependent mechanism, which in turn drives the synaptic delivery of homomeric GluA1 receptors. Impairment of SNX27 prevents LTP and associated trafficking of AMPARs. These results demonstrate a role for SNX27 in neuronal plasticity, provide a molecular explanation for the K-ras signal during LTP and identify SNX27 as the PDZ-containing molecular linker that couples the plasticity stimuli to the delivery of postsynaptic cargo.
1] Institute of Molecular and Cell Biology, Singapore 138673, Singapore [2] Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 637553, Singapore.
Li Shen
LS
Loo
Department of Pharmacology, Neurobiology and Ageing Programme, Singapore Institute for Neurotechnology, National University of Singapore, Singapore 117597, Singapore.
Ning
N
Tang
Institute of Molecular and Cell Biology, Singapore 138673, Singapore.
Muthafar
M
Al-Haddawi
Department of Pharmacology, Neurobiology and Ageing Programme, Singapore Institute for Neurotechnology, National University of Singapore, Singapore 117597, Singapore.
Gavin Stewart
GS
Dawe
1] Institute of Molecular and Cell Biology, Singapore 138673, Singapore [2] Department of Biochemistry, National University of Singapore, Singapore 117597, Singapore.
Wanjin
W
Hong
D000818:Animals; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D021381:Protein Transport; D018091:Receptors, AMPA / Q000378:metabolism*; D058305:Sorting Nexins / Q000502:physiology*
D018091:Receptors, AMPA; D058305:Sorting Nexins