FHOD1 interaction with nesprin-2G mediates TAN line formation and nuclear movement

• Published in: Nature cell biology Vol. 16; no. 7; pp. 708 - 715
• Main Authors: Kutscheidt, Stefan, Zhu, Ruijun, Antoku, Susumu, Luxton, G. W. Gant, Stagljar, Igor, Fackler, Oliver T., Gundersen, Gregg G.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.07.2014; Nature Publishing Group
• Subjects: 13; 13/89; 14; 14/1; 14/35; 631/80/128/1276; 631/80/642/1363; 631/80/85; Actins - metabolism; Animals; Antibodies; Binding sites; Biology; Blotting, Western; Cables; Cancer Research; Cell Biology; Cell division; Cell interaction; Cell Nucleus - metabolism; Cell research; Cells, Cultured; Cellular proteins; Centrosome - metabolism; Developmental Biology; Fetal Proteins - genetics; Fetal Proteins - metabolism; Gene Silencing; Genetic aspects; HEK293 Cells; Humans; letter; Life Sciences; Mammals; Membrane Proteins - metabolism; Mice; Microfilament Proteins - metabolism; Nerve Tissue Proteins - metabolism; NIH 3T3 Cells; Nuclear Envelope - metabolism; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Properties; Protein Binding; Stem Cells; Translocation; Yeast; New York; United States > US
• ISSN: 1465-7392; 1476-4679
• DOI: 10.1038/ncb2981

Gundersen and colleagues report that the FHOD1 formin is involved in nuclear positioning, by physically linking nesprin-2G, a protein of the outer nuclear membrane, to actin cables, to allow the formation of the transmembrane actin-associated nuclear (TAN) lines that are needed to move the nucleus. Active positioning of the nucleus is integral to division, migration and differentiation of mammalian cells 1 . Fibroblasts polarizing for migration orient their centrosomes by actin-dependent nuclear movement 2 . This nuclear movement depends on nesprin-2 giant (N2G), a large, actin-binding outer nuclear membrane component of transmembrane actin-associated (TAN) lines that couple nuclei to moving actin cables 3 . Here, we identify the diaphanous formin FHOD1 as an interaction partner of N2G. Silencing FHOD1 expression or expression of fragments containing binding sites for N2G or FHOD1 disrupted nuclear movement and centrosome orientation in polarizing fibroblasts. Unexpectedly, silencing of FHOD1 expression did not affect the formation or rearward flow of dorsal actin cables required for nuclear positioning. Rather, N2G–FHOD1 interaction provided a second connection to actin cables essential for TAN line formation and thus nuclear movement. These results reveal a unique function for a formin in coupling an organelle to actin filaments for translocation, and suggest that TAN lines require multi-point attachments to actin cables to resist the large forces necessary to move the nucleus.