Splice variant-specific cellular function of the formin INF2 in maintenance of Golgi architecture

Vinay Ramabhadran, Farida Korobova, Gilbert J. Rahme, Henry N. Higgs*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

67 Scopus citations


INF2 is a unique formin that can both polymerize and depolymerize actin filaments. Mutations in INF2 cause the kidney disease focal and segmental glomerulosclerosis. INF2 can be expressed as two C-terminal splice variants: CAAX and non-CAAX. The CAAX isoform contains a C-terminal prenyl group and is tightly bound to endoplasmic reticulum (ER). The localization pattern and cellular function of the non-CAAX isoform have not been studied. Here we find that the two isoforms are expressed in a cell type-dependent manner, with CAAX predominant in 3T3 fibroblasts and non-CAAX predominant in U2OS, HeLa, and Jurkat cells. Although INF2-CAAX is ER localized in an actin-independent manner, INF2-non-CAAX localizes in an actin-dependent meshwork pattern distinct from ER. INF2-non-CAAX is loosely attached to this meshwork, being extracted by brief digitonin treatment. Suppression of INF2-non-CAAX causes fragmentation of the Golgi apparatus. This effect is counteracted by treatment with the actin monomer-sequestering drug latrunculin B. We also find discrete patches of actin filaments in the peri-Golgi region, and these patches are reduced upon INF2 suppression. Our results suggest that the non-CAAX isoform of INF2 serves a distinct cellular function from that of the CAAX isoform.

Original languageEnglish (US)
Pages (from-to)4822-4833
Number of pages12
JournalMolecular biology of the cell
Issue number24
StatePublished - Dec 15 2011

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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