Abstract
During synaptic scaling up, a transcription-dependent process, a drop in firing rates will\r lead to a change in transcription of “scaling factors” which will induce an increase in synaptic\r AMPAR accumulation at synaptic sites. In order to determine the genes for which transcription\r is either up or down-regulated during synaptic scaling up, an unbiased transcriptional screen was\r performed. Among the different transcript hits is SAP97, a synapse associated protein implicated\r in receptor trafficking, and specifically, is shown to have a role in trafficking AMPA receptors at\r the synapse. This protein binds to the GluA1 subunit of AMPA receptors, and traffics it from the\r Golgi body to the plasma membrane. To confirm the finding of the screen, we tested whether\r SAP97 is up-regulated during synaptic scaling in vitro. We found that SAP97 expression is upregulated\r during synaptic scaling and is also transcription dependent. We also stained for GluA2,\r another subunit of AMPA receptors, to learn about SAP97 potential role in synaptic scaling and\r found that SAP97 may also function in conjunction with GluA2 during synaptic scaling.\r Additionally, SAP97 is active downstream of CAMKIV in the mechanistic pathway of synaptic\r scaling. This additionally strongly suggests that SAP97 may have an important role in synaptic\r scaling, but needs to be further tested.