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Mutations in the
nuclear membrane genes lead to cardiomyopathy and muscular dystrophy. Lamin A/C is an intermediate filament
protein associated with the inner nuclear membrane. Mutations in the Lamin A/C gene lead to cardiac and skeletal
muscle degeneration. More recently, lamin A/C gene mutations have been
implicated in other disorders including lipodystrophy and aging. Mutations in the gene encoding
emerin, another nuclear membrane protein gene, also lead to a cardiomyopathy
and muscular dystrophy indicating that the nuclear membrane is particularly
critical for heart and skeletal muscle.
We identified nesprin-1 (also called syne-1 or myne-1) as a binding
partner of lamin and emerin. We
hypothesize that disruption of the nuclear membrane may lead to alterations
in gene expression, altered heterochromatin and changes in signaling cascades
producing cardiomyopathy and muscular dystrophy. Shown above is a section from the heart showing nesprin-1
at the nuclear membrane in red and dystrophin at the plasma membrane in
green.
References:
Mislow,
J. M., M. Kim, D. Belt Davis and E. M. McNally. Myne-1, a spectrin repeat protein of the inner nuclear
membrane, associates with lamin. (2002) J. Cell Science 115:61-70.
Mislow,
J. M., J. Holuska, M. S. Kim, K. K. Lee, M. Segura-Totten, K. L. Wilson and
E. M. McNally. Nesprin-1a (myne-1) self-associates and
binds directly to emerin and lamin A in vitro. (2002) FEBS Lett. 525:135-140.
Muchir, A., B. Van Engelen, M.
Lammens, J. M. Mislow, E. McNally, K. Schwartz, and G. Bonne. Nuclear envelope alterations in fibroblasts from
LGMD1B patients carrying nonsense Y259X heterozygous or homozygous mutation
in lamin A/C gene. (2003) Exp
Cell Res. 291:352-62.
MacLeod,
H. M., M. R. Culley, J. M. Huber and E. M. McNally. Lamin A/C truncation associated with dilated
cardiomyopathy and conduction system disease. (2003) BMC Med Genet 4:4.
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