Actin-associated neurabin-protein phosphatase-1 complex regulates hippocampal plasticity.
Protein phosphatase-1 (PP1) has been implicated in the control of long-term potentiation (LTP) and depression (LTD) in rat hippocampal CA1 neurons. PP1 catalytic subunits associate with multiple postsynaptic regulatory subunits, but the PP1 complexes that control hippocampal LTP and LTD in the rat hippocampus remain unidentified. The neuron-specific actin-binding protein, neurabin-I, is enriched in dendritic spines, and tethers PP1 to actin-rich postsynaptic density to regulate morphology and maturation of spines. The present studies utilized Sindbis virus-mediated expression of wild-type and mutant neurabin-I polypeptides in organotypic cultures of rat hippocampal slices to investigate their role in synaptic plasticity. While wild-type neurabin-I elicited no change in basal synaptic transmission, it enhanced LTD and inhibited LTP in CA1 pyramidal neurons. By comparison, mutant neurabins, specifically those unable to bind PP1 or F-actin, decreased basal synaptic transmission, attenuated LTD and increased LTP in slice cultures. Biochemical and cell biological analyses suggested that, by mislocalizing synaptic PP1, the mutant neurabins impaired the functions of endogenous neurabin-PP1 complexes and modulated LTP and LTD. Together, these studies provided the first biochemical and physiological evidence that a postsynaptic actin-bound neurabin-I-PP1 complex regulates synaptic transmission and bidirectional changes in hippocampal plasticity.
Hu
Xiao Dong
XD
Neuroscience Center of Excellence, LSU Health Science Center, New Orleans, Louisiana, USA.
Huang
Qing
Q
Roadcap
David W
DW
Shenolikar
Shirish S
SS
Xia
Houhui
H
D000199:Actins / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D049452:Green Fluorescent Proteins; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000502:physiology; D049408:Luminescent Agents; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism / Q000502:physiology*; D054645:Protein Phosphatase 1; D051381:Rats; D009435:Synaptic Transmission / Q000502:physiology; D014018:Tissue Distribution; D000099273:Neurabins
D000199:Actins; D049452:Green Fluorescent Proteins; D049408:Luminescent Agents; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D000099273:Neurabins