Quantitative Multiplex Immunoprecipitation (QMI) analysis of protein interaction network rearrangements during homeostatic plasticity

Neurons maintain constant levels of excitability using homeostatic
synaptic scaling, which adjusts the strength of all of a neuron’s
postsynaptic inputs to compensate for large changes in overall activity.
Here, we asked how prolonged changes in activity affect network-level
protein interactions at the synapse. We assessed a glutamatergic synapse
protein interaction network (PIN) composed of 380 binary associations
among 21 protein members to identify protein complexes altered by activity
manipulation in vitro or sensory deprivation in vivo. In cultured cortical
neurons, we observed widespread bidirectional PIN alterations during up-
and downscaling that reflected rapid rearrangements of glutamate receptor
co-associations via synaptic scaffold remodeling. Sensory
deprivation of the barrel cortex caused unique PIN rearrangements,
including changes in co-associations between the glutamate
receptor mGluR5 and the kinase Fyn, consistent with emerging models of
experience dependent plasticity involving multiple types of homeostatic
responses. Mice lacking Homer1 or Shank3B did not undergo normal PIN
rearrangements, suggesting that these Autism Spectrum Disorder
(ASD)-linked proteins serve as structural hubs for synaptic homeostasis.
This dataset contains the raw XML and PBX (bioplex protocol) files
necessary for performing adaptive non-parametric analysis with an emprical
alpha cutoff (ANC) to identify high-confidence IP_Probe pairs,
here called "PiSCES" for proteins in shared complexes detected
by surface epitopes, that are signifianctly differently
associated between two conditions.