KASHing up with the nucleus: novel functional roles of KASH proteins at the cytoplasmic surface of the nucleus.

Nuclear-cytoskeletal connections are central to fundamental cellular processes, including nuclear positioning and chromosome movements in meiosis. The cytoskeleton is coupled to the nucleoskeleton through conserved KASH-SUN bridges, or LINC complexes, that span the nuclear envelope. KASH proteins localize to the outer nuclear membrane where they connect the nucleus to the cytoskeleton. New findings have expanded the functional diversity of KASH proteins, showing that they interact with microtubule motors, actin, intermediate filaments, a nonconventional myosin, RanGAP, and each other. The role of KASH proteins in cellular mechanics is discussed. Genetic mutations in KASH proteins are associated with autism, hearing loss, cancer, muscular dystrophy and other diseases.