Data from: Cypin regulates K63-linked polyubiquitination to shape synaptic content

An open question in neuroscience is how protein posttranslational
modifications regulate synaptic site targeting. Polyubiquitination plays a
role in proteasome-mediated protein turnover; however, additional
functions for specific types of polyubiquitin linkages have been
identified. One type of polyubiquitination, K63-polyubiquitin
(K63-polyUb), has been studied for its role in signal transduction within
the context of cancer, but little has been done to uncover its role
regarding neuronal and synaptic function. Here, we report an emerging
function for the cytosolic PSD-95 interactor, cypin, in the regulation of
synaptic content by K63-polyUb during neuronal development in vitro and in
adult mice in vivo. We identify cypin-promoted K63-polyUb on postsynaptic
proteins and also find an important role for cypin in presynaptic
function. Our work demonstrates for the first time that cypin-promoted
changes to K63-polyUb can regulate synaptic content and function on both
sides of the synapse, adding important insight into basic mechanisms of
neuronal signaling.