Deficiency of cks1 leads to learning and long-term memory defects and p27 dependent formation of neuronal cofilin aggregates

Alexander Kukalev, Yiu Ming Ng, Limei Ju, Amal Saidi, Sophie Lane, Angeles Mondragon, Dirk Dormann, Sophie E. Walker, William Grey, Philip Wing Lok Ho, David N. Stephens, Antony M. Carr, Karri Lamsa, Eric Tse, Veronica P.C.C. Yu

Research output: Journal article publicationJournal articleAcademic researchpeer-review

4 Citations (Scopus)


In mitotic cells, the cyclin-dependent kinase (CDK) subunit protein CKS1 regulates S phase entry by mediating degradation of the CDK inhibitor p27. Although mature neurons lack mitotic CDKs, we found that CKS1 was actively expressed in post-mitotic neurons of the adult hippocampus. Interestingly, Cks1 knockout (Cks1/) mice exhibited poor long-term memory, and diminished maintenance of long-term potentiation in the hippocampal circuits. Furthermore, there was neuronal accumulation of cofilin-actin rods or cofilin aggregates, which are associated with defective dendritic spine maturation and synaptic loss. We further demonstrated that it was the increased p27 level that activated cofilin by suppressing the RhoA kinase-mediated inhibitory phosphorylation of cofilin, resulting in the formation of cofilin aggregates in the Cks1−/− neuronal cells. Consistent with reports that the peptidyl-prolyl-isomerase PIN1 competes with CKS1 for p27 binding, we found that inhibition of PIN1 diminished the formation of cofilin aggregates through decreasing p27 levels, thereby activating RhoA and increasing cofilin phosphorylation. Our results revealed that CKS1 is involved in normal glutamatergic synapse development and dendritic spine maturation in adult hippocampus through modulating p27 stability.

Original languageEnglish
Pages (from-to)11-23
Number of pages13
JournalCerebral Cortex
Issue number1
Publication statusPublished - 1 Jan 2017
Externally publishedYes


  • Cyclin-dependent kinase
  • Hippocampus
  • Long-term potentiation
  • RhoA
  • Synaptic plasticity

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience


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