The actin-binding domain of spinophilin is necessary and sufficient for targeting to dendritic spines.
Spinophilin is enriched in dendritic spines, small protrusions of the postsynaptic membrane along the length of the dendrite that contain the majority of excitatory synapses. Spinophilin binds to protein phosphatase 1 with high affinity and targets it to dendritic spines, therefore placing it in proximity to regulate glutamate receptor activity. Spinophilin also binds to and bundles f-actin, the main cytoskeletal constituent of dendritic spines, and may therefore serve to regulate the structure of the synapse. In this study, we sought to determine the structural basis for the targeting of spinophilin to dendritic spines. Our results show that the actin-binding domain of spinophilin is necessary and sufficient for targeting of spinophilin to dendrites and dendritic spines.
Grossman
Stacie D
SD
Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10021, USA. grossms@rockefeller.edu
Hsieh-Wilson
Linda C
LC
Allen
Patrick B
PB
Nairn
Angus C
AC
Greengard
Paul
P
D000199:Actins / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D007668:Kidney; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D009842:Oligopeptides; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000032:analysis / Q000235:genetics; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D054645:Protein Phosphatase 1; D017434:Protein Structure, Tertiary; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D017384:Sequence Deletion; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure; D014162:Transfection; D000099273:Neurabins
D000199:Actins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D009842:Oligopeptides; D010446:Peptide Fragments; D010455:Peptides; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D011993:Recombinant Fusion Proteins; D000099273:Neurabins; C085706:FLAG peptide