Role of Nuclear Envelope Proteins in the Structure and Function of the Neuromuscular Junction: Focus on Subsynaptic Nuclei.

The role of the nuclear envelope (NE) in skeletal muscle function was first recognized 30 years ago when mutations in NE-associated genes, such as SUN-1, Syne1, Syne2, and LMNA, were linked to muscular dystrophies, also known as nuclear envelopathies. These findings underscored the critical role of NE components in maintaining muscle fiber integrity and function. NE proteins, including lamin A/C, SUN-1/2, nesprins, and LAP1, play a key role in anchoring and positioning nuclei within muscle fibers. In particular, the correct positioning of subsynaptic nuclei (SSNs) beneath the neuromuscular junction (NMJ) is essential for their differentiation and functional specialization, ensuring efficient neuromuscular transmission. The crucial role of the NE in SSNs and NMJ function has been further emphasized by its association with an atypical form of congenital myasthenic syndrome (CMS). Despite significant advances in understanding NMJ formation and motor neuron-myofiber communication, the mechanisms governing gene regulation in SSNs remain largely unexplored.