Requirement for protein synthesis at developing synapses

Joseph Sebeo, Kuangfu Hsiao, Ozlem Bozdagi, Dani Dumitriu, Yongchao Ge, Qiang Zhou, Deanna L. Benson

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Activity and protein synthesis act cooperatively to generate persistent changes in synaptic responses. This forms the basis for enduring memory in adults. Activity also shapes neural circuits developmentally, but whether protein synthesis plays a congruent function in this process is poorly understood. Here,weshow that brief periods of global or local protein synthesis inhibition decrease the synaptic vesicles available for fusion and increase synapse elimination. Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a critical target; its levels are controlled by rapid turnover, and blocking its activity or knocking it down recapitulates the effects of protein synthesis inhibition. Mature presynaptic terminals show decreased sensitivity to protein synthesis inhibition, and resistance coincides with a developmental switch in regulation from CaMKII to PKA (protein kinase A). These findings demonstrate a novel mechanism regulating presynaptic activity and synapse elimination during development, and suggest that protein translation acts coordinately with activity to selectively stabilize appropriate synaptic interactions.

Original languageEnglish (US)
Pages (from-to)9778-9793
Number of pages16
JournalJournal of Neuroscience
Volume29
Issue number31
DOIs
StatePublished - Aug 5 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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