Document Type

Article

Publication Date

10-6-2011

Publication Title

Molecular Biology of the Cell

Department

Geisel School of Medicine

Abstract

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.

DOI

10.1091/mbc.E11-05-0457

Original Citation

Ramabhadran V, Korobova F, Rahme GJ, Higgs HN. Splice variant-specific cellular function of the formin INF2 in maintenance of Golgi architecture. Mol Biol Cell. 2011 Dec;22(24):4822-33. doi: 10.1091/mbc.E11-05-0457. Epub 2011 Oct 12. PMID: 21998196; PMCID: PMC3237625.

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