Abstract: The nuclear lamina, along with associated nuclear membrane proteins, is a nexus for regulating
signaling in the nucleus. Numerous human diseases arise from mutations in lamina
proteins, and experimental models for these disorders have revealed aberrant regulation of
various signaling pathways. Previously, we reported that the inner nuclear membrane protein
Lem2, which is expressed at high levels in muscle, promotes the differentiation of cultured
myoblasts by attenuating ERK signaling. Here, we have analyzed mice harboring a
disrupted allele for the Lem2 gene (Lemd2). No gross phenotypic defects were seen in heterozygotes,
although muscle regeneration induced by cardiotoxin was delayed. By contrast,
homozygous Lemd2 knockout mice died by E11.5. Although many normal
morphogenetic hallmarks were observed in E10.5 knockout embryos, most tissues were
substantially reduced in size. This was accompanied by activation of multiple MAP kinases
(ERK1/2, JNK, p38) and AKT. Knockdown of Lem2 expression in C2C12 myoblasts also
led to activation of MAP kinases and AKT. These findings indicate that Lemd2 plays an essential
role in mouse embryonic development and that it is involved in regulating several signaling
pathways. Since increased MAP kinase and AKT/mTORC signaling is found in other
animal models for diseases linked to nuclear lamina proteins, LEMD2 should be considered
to be another candidate gene for human disease.
Fuente: PLoS One
. 2015 Mar 19;10(3):e0116196
Editorial: Public Library of Science
Año de publicación: 2015
Nº de páginas: 20
Tipo de publicación: Artículo de Revista
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OLGA TAPIA MARTINEZ
FONG, LOREN G.
HUBER, MICHAEL D.
YOUNG, STEPHEN G.