Mutations in LMNA, which encodes A-type nuclear lamins, cause at least 13 human hereditary diseases. These ‘laminopathies’ include several myopathies, lipodystrophy and progeria, but how do mutations in one gene cause all these disorders? On page 3893, Yukiko Hayashi and colleagues identify a disease-related phosphorylation site in A-type lamins that throws some light on this puzzle. Human A-type lamins contain more than 30 phosphorylation sites. To investigate the physiological importance of these sites, the authors made site- and phosphorylation-state-specific antibodies against human A-type lamins. An antibody that recognises phosphorylated Ser458 reacts with nuclei in muscle biopsies from patients with myopathy caused by mutations in the immunoglobulin-like fold motif of A-type lamins, they report, but not with biopsies from patients with other neuromuscular diseases. Furthermore, myopathy-related LMNA mutations induce Ser458 phosphorylation by Akt1 in vitro, but LMNA mutations related to lipodystrophy or progeria do not induce Ser458 phosphorylation. The...

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