GluR1 controls dendrite growth through its binding partner, SAP97.
Activity-dependent dendrite elaboration influences the pattern of interneuronal connectivity and network function. In the present study, we examined the mechanism by which the GluR1 subunit of AMPA receptors controls dendrite morphogenesis. GluR1 binds to SAP97, a scaffolding protein that is a component of the postsynaptic density, via its C-terminal 7 aa. We find that elimination of this interaction in vitro or in vivo (by deleting the C-terminal 7 aa of GluR1, GluR1Delta7) does not influence trafficking, processing, or cell surface GluR1 expression but does prevent translocation of SAP97 from the cytosol to membranes. GluR1 and SAP97 together at the plasma membrane promotes dendrite branching in an activity-dependent manner, although this does not require physical association. Our findings suggest that the C-terminal 7 aa of GluR1 are essential for bringing SAP97 to the plasma membrane, where it acts to translate the activity of AMPA receptors into dendrite growth.
Department of Pediatrics, Division of Neurology, Joseph Stokes Jr. Research Institute, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Weiguo
W
Zhou
Lei
L
Zhang
Xiong
X
Guoxiang
Jelena
J
Mojsilovic-Petrovic
Kogo
K
Takamaya
Rita
R
Sattler
Richard
R
Huganir
Robert
R
Kalb
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002678:Chimera; D003712:Dendrites / Q000378:metabolism / Q000502:physiology*; D000074288:Discs Large Homolog 1 Protein; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009046:Motor Neurons / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D018091:Receptors, AMPA / Q000378:metabolism*; D013116:Spinal Cord / Q000502:physiology* / Q000648:ultrastructure
D048868:Adaptor Proteins, Signal Transducing; D000074288:Discs Large Homolog 1 Protein; D008565:Membrane Proteins; D018091:Receptors, AMPA; C513314:DLG1 protein, human