(339b) Nuclear Cytoskeletal Linkages Are Required for Normal Cell Function

Introduction: The linker of nucleoskeleton and cytoskeleton (LINC) complex, which is composed of outer nuclear membrane proteins Klarsicht, ANC-1, and Syne homology (KASH) and inner nuclear membrane proteins, Sad1 and UNC-84, transmits mechanical forces from the cytoskeleton to the nucleus. Here we asked if an intact LINC complex is required for normal cell function.

Result: The LINC complex has been proposed to transmit forces required for nuclear shaping. However, we did not find differences in nuclear shapes between control cells and LINC-disrupted cells. Although LINC complex disruption did not affect the nuclear shaping, we found that LINC disrupted MCF10A cells failed to form normal acini with clear lumens. Unlike WT cells, LINC disrupted cells failed to heal wounds in a wound healing assay. LINC disrupted fibroblasts also were unable to migrate. The lack of migration however did not correlate with changes in ROCK-Rho-CDC42 activities in fibroblasts.

Conclusion: An intact LINC complex is required for normal cell migration and tissue development, but not for nuclear shaping in MCF10A cells. We propose that mechanical force transmission by the LINC complex to the nucleus allows cells to migrate efficiently, which may explain the observed effects of LINC disruption on migration and tissue development.