Neuronal IP3 3-kinase is an F-actin-bundling protein: Role in dendritic targeting and regulation of spine morphology

Hong W. Johnson, Michael J. Schell

Research output: Contribution to journalArticlepeer-review

87 Scopus citations


The actin microstructure in dendritic spines is involved in synaptic plasticity. Inositol trisphosphate 3-kinase A (ITPKA) terminates Ins(1,4,5)P3 signals emanating from spines and also binds filamentous actin (F-actin) through its amino terminal region (amino acids 1-66, N66). Here we investigated how ITPKA, independent of its kinase activity, regulates dendritic spine F-actin microstructure. We show that the N66 region of the protein mediates F-actin bundling. An N66 fusion protein bundled F-actin in vitro, and the bundling involved N66 dimerization. By mutagenesis we identified a point mutation in a predicted helical region that eliminated both F-actin binding and bundling, rendering the enzyme cytosolic. A fusion protein containing a minimal helical region (amino acids 9-52, N9-52) bound F-actin in vitro and in cells, but had lower affinity. In hippocampal neurons, GFP-tagged N66 expression was highly polarized, with targeting of the enzyme predominantly to spines. By contrast, N9-52-GFP expression occurred in actin-rich structures in dendrites and growth cones. Expression of N66-GFP tripled the length of dendritic protrusions, induced longer dendritic spine necks, and induced polarized actin motility in time-lapse assays. These results suggest that, in addition to its ability to regulate intracellular Ca2+ via Ins(1,4,5)P3 metabolism, ITPKA regulates structural plasticity.

Original languageEnglish (US)
Pages (from-to)5166-5180
Number of pages15
JournalMolecular biology of the cell
Issue number24
StatePublished - 2009
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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