Regulation of SAP102 Synaptic Targeting by Phosphorylation

Zhe Wei, Guangyu Wu, Bo-Shiun Chen

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Synapse-associated protein 102 (SAP102) is a scaffolding protein highly expressed early in development and plays a critical role in mediating glutamate receptor trafficking during synaptogenesis. Mutations in human SAP102 have been reported to cause intellectual disability, which is thought to be due to mislocalization of the mutant protein. However, little is known about the regulation of SAP102 synaptic targeting. Here, we investigate the role of phosphorylation of SAP102 in regulating its synaptic targeting. Previous studies have shown that synaptic targeting of SAP102 is regulated by C-terminal splicing. We now identify a phosphorylation site, serine 632, within the C-terminal alternatively spliced region, which is phosphorylated by casein kinase II (CK2). We show that Ser632 on SAP102 is phosphorylated in vitro, in heterologous cells, and in neurons. Moreover, we demonstrate that synaptic enrichment of SAP102 is increased by Ser632 phosphorylation. Consistently, elevation of synaptic activity that suppresses Ser632 phosphorylation reduces synaptic enrichment of SAP102. Furthermore, the mobility of SAP102 is decreased by Ser632 phosphorylation. Therefore, not only SAP102 synaptic targeting but also its mobility is regulated by Ser632 phosphorylation. These data provide evidence for a novel mechanism in regulating SAP102 function and glutamate receptor trafficking.

Original languageEnglish (US)
Pages (from-to)6215-6226
Number of pages12
JournalMolecular Neurobiology
Volume55
Issue number8
DOIs
StatePublished - Aug 1 2018

Fingerprint

Synapses
Phosphorylation
Proteins
Glutamate Receptors
Casein Kinase II
Mutant Proteins
Intellectual Disability
Serine
Neurons
Mutation

Keywords

  • CK2
  • Glutamate
  • Intellectual disability
  • MAGUK
  • Phosphorylation

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Regulation of SAP102 Synaptic Targeting by Phosphorylation. / Wei, Zhe; Wu, Guangyu; Chen, Bo-Shiun.

In: Molecular Neurobiology, Vol. 55, No. 8, 01.08.2018, p. 6215-6226.

Research output: Contribution to journalArticle

Wei, Zhe ; Wu, Guangyu ; Chen, Bo-Shiun. / Regulation of SAP102 Synaptic Targeting by Phosphorylation. In: Molecular Neurobiology. 2018 ; Vol. 55, No. 8. pp. 6215-6226.
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