Cofilin aggregation blocks intracellular trafficking and induces synaptic loss in hippocampal neurons

Joseph Cichon, Chicheng Sun, Ben Chen, Min Jiang, Xiangyun Amy Chen, Yajie Sun, Yun Wang, Gong Chen

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Cofilin is an actin-binding protein and a major actin depolymerization factor in the central nervous system (CNS). Cofilin-actin aggregates are associated with neurodegenerative disorders, but how cofilin-actin aggregation induces pathological effects in the CNS remains unclear. Here, we demonstrated that cofilin rods disrupted dendritic microtubule integrity in rat hippocampal cultures. Long term time-lapse imaging revealed that cofilin rods block intracellular trafficking of both mitochondria and early endosomes. Importantly, cofilin rod formation induced a significant loss of SV2 and PSD-95 puncta as well as dendritic spines. Cofilin rods also impaired local glutamate receptor responses. We discovered an inverse relationship between the number of synaptic events and the accumulation of cofilin rods in dendrites. We also detected cofilin rods in aging rat brains in vivo. These results suggest that cofilin aggregation may contribute to neurodegeneration and brain aging by blocking intracellular trafficking and inducing synaptic loss.

Original languageEnglish (US)
Pages (from-to)3919-3929
Number of pages11
JournalJournal of Biological Chemistry
Volume287
Issue number6
DOIs
StatePublished - Feb 3 2012

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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