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

Abstract

INF2 is a unique formin that can both polymerize and depolymerize actin. One INF2 splice variant localizes in an actin-dependent, web-like network in cytoplasm, whereas a second isoform is ER bound. Suppression of the first isoform causes Golgi dispersion. These findings denote isoform-specific cellular functions for INF2.

Assembly and Turnover of Short Actin Filaments by the Formin INF2 and Profilin

“…Given that a cytosolic isoform, INF2-non-CAAX, participates in Golgi dynamics (4), it is possible that INF2-generated short, transient actin filaments might be used in other organellar membrane fission processes. Indeed, small actin "puncta" are present at the trans-Golgi network (4, 6), and we have found that the puncta number decreases upon INF2 suppression (4). Other proteins, such as Cordon Bleu, might play similar roles for other actin-based processes.…”

“…The cytosolic concentration of INF2 is much lower, ranging from 10 to 100 nM in the cytosol from quantitative immune-blotting experiments. 3 In addition, the two distinct splice variants of INF2 have very different localization patterns (4,47). However, local enrichment of INF2, such as on the ER membrane, might drive short filament assembly.…”

“…In cells, INF2 acts in multiple processes, but the best understood is its role in mitochondrial fission, in which endoplasmic reticulum-bound INF2 assembles filaments that facilitate fission (26). INF2 is likely to have similar roles in other cytoplasmic actin-based processes (4). This paper focuses on the biochemical mechanism behind the ability of INF2 to accelerate filament depolymerization.…”

Actin Monomers Activate Inverted Formin 2 by Competing with Its Autoinhibitory Interaction

“…whereas the INF2-non-CAAX variant is cytoplasmic and plays a role in Golgi organization (18). INF2 may play additional roles in vesicular trafficking, microtubule stabilization, and centrosome orientation (19 -21).…”

Mutations to the Formin Homology 2 Domain of INF2 Protein Have Unexpected Effects on Actin Polymerization and Severing

“…The CAAX variant binds tightly to endoplasmic reticulum (ER) and overexpression causes ER collapse (21). The non-CAAX variant localizes in a cytoplasmic, actin-dependent meshwork pattern, and its suppression causes Golgi fragmentation (22). Suppression of INF2 in hepatocytic culture cells results in defects in transcytosis of apical proteins (23), whereas suppression in lymphocytic cells inhibits delivery of Lck to the plasma membrane (24).…”