A role for sorting nexin 27 in AMPA receptor trafficking

• Published in: Nature communications Vol. 5; no. 1; p. 3176
• Main Authors: Loo, Li Shen, Tang, Ning, Al-Haddawi, Muthafar, Stewart Dawe, Gavin, Hong, Wanjin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24-01-2014; Nature Publishing Group; Nature Pub. Group
• Subjects: 13; 14; 631/378/2591; 631/378/340; 631/80/313; 631/80/86; 82; Animals; Brain; Humanities and Social Sciences; Humans; Hydrocephalus; Mice; Mice, Knockout; multidisciplinary; Neurosciences; Protein Transport; Proteins; Receptors, AMPA - metabolism; Science; Science (multidisciplinary); Sorting Nexins - physiology; Singapore
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms4176

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.
Sorting nexin 27 (SNX27) regulates endosomal sorting of glutamate receptors. Loo
et al.
show that SNX27 is localized to recycling endosomes within dendritic spines where it interacts with glutamate receptors, allowing them to be shuttled to the postsynaptic membrane.