Syne-1, a dystrophin- and klarsicht-related protein associated with synaptic nuclei at the neuromuscular junction

We describe a novel protein, Syne-1, that is associated with nuclear envelopes in skeletal, cardiac, and smooth muscle cells. Syne-1 contains multiple spectrin repeats similar to those found in dystrophin and utrophin, as well as a domain homologous to the carboxyl-terminal of Klarsicht, a protein associated with nuclei and required for a subset of nuclear migrations in Drosophila. In adult skeletal muscle fibers, levels of Syne-1 are highest in the nuclei that lie beneath the postsynaptic membrane at: the neuromuscular junction. These nuclei are transcriptionally specialized, expressing genes for synaptic components at higher levels than extrasynaptic nuclei in the same cytoplasm. Syne-1 is the first protein found to be selectively associated with synaptic nuclei. Syne-1 becomes concentrated in synaptic nuclei postnatally. It remains synaptically enriched following denervation or degeneration/regeneration, and is also present at high levels in the central nuclei of dystrophic myotubes. The location and structure of Syne-1 suggest that it may participate in the migration of myonuclei in myotubes and/or their anchoring at the postsynaptic apparatus. Finally, we identify a homologous gene, syne-2, that is expressed in an overlapping but distinct pattern.