Role of ANC-1 in tethering nuclei to the actin cytoskeleton

Starr et al. (2002). Science DOI: 10.1126/science.1075119 Citations: 414

Parts used

KASH Domain

Key findings

  • Defined the KASH (Klarsicht/ANC-1/Syne Homology) domain as the conserved C-terminal transmembrane domain responsible for outer nuclear membrane localization and nuclear envelope anchoring to the cytoskeleton. Established the LINC complex paradigm. KASH domains are used to anchor proteins to the outer nuclear membrane in engineered systems.

Abstract

Mutations in anc-1 (nuclear anchorage defective) disrupt the positioning of nuclei and mitochondria in Caenorhabditis elegans. ANC-1 is shown to consist of mostly coiled regions with a nuclear envelope localization domain (called the KASH domain) and an actin-binding domain; this structure was conserved with the Drosophila protein Msp-300 and the mammalian Syne proteins. Antibodies against ANC-1 localized cytoplasmically and were enriched at the nuclear periphery in an UNC-84-dependent manner. Overexpression of the KASH domain or the actin-binding domain caused a dominant negative anchorage defect. Thus, ANC-1 may connect nuclei to the cytoskeleton by interacting with UNC-84 at the nuclear envelope and with actin in the cytoplasm.