Assuntos
Dor Abdominal/etiologia , Infecções por Chlamydia/diagnóstico , Cisto do Colédoco/diagnóstico por imagem , Insuficiência de Crescimento/etiologia , Hepatite/diagnóstico , Hiperbilirrubinemia/etiologia , Doença Inflamatória Pélvica/diagnóstico , Peritonite/diagnóstico , Imunodeficiência Combinada Severa/diagnóstico , Adolescente , Antibacterianos/uso terapêutico , Infecções por Chlamydia/complicações , Infecções por Chlamydia/tratamento farmacológico , Cisto do Colédoco/cirurgia , Diagnóstico Diferencial , Doxiciclina/uso terapêutico , Feminino , Hepatite/complicações , Hepatite/tratamento farmacológico , Humanos , Lactente , Masculino , Doença Inflamatória Pélvica/complicações , Doença Inflamatória Pélvica/tratamento farmacológico , Peritonite/complicações , Peritonite/tratamento farmacológico , Imunodeficiência Combinada Severa/terapia , UltrassonografiaRESUMO
Nesprin-1alpha is a spectrin repeat (SR)-containing, transmembrane protein of the inner nuclear membrane, and is highly expressed in muscle cells. A yeast two-hybrid screen for nesprin-1alpha-interacting proteins showed that nesprin-1alpha interacted with itself. Blot overlay experiments revealed that nesprin-1alpha's third SR binds the fifth SR. The carboxy-terminal half of nesprin-1alpha directly bound lamin A, a nuclear intermediate filament protein. Biochemical analysis demonstrated that nesprin-1alpha dimers bind directly to the nucleoplasmic domain of emerin, an inner nuclear membrane protein, with an affinity of 4 nM. Binding was optimal for full nucleoplasmic dimers of nesprin-1alpha, since nesprin fragments SR1-5 and SR5-7 bound emerin as monomers with affinities of 53 nM and 250 mM, respectively. We propose that membrane-anchored nesprin-1alpha antiparallel dimers interact with both emerin and lamin A to provide scaffolding at the inner nuclear membrane.
Assuntos
Proteínas de Transporte/metabolismo , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso , Proteínas Nucleares/metabolismo , Proteínas de Saccharomyces cerevisiae , Timopoietinas/metabolismo , Proteínas do Citoesqueleto , Proteínas de Ligação a DNA/metabolismo , Dimerização , Humanos , Lamina Tipo A , Laminas , Membrana Nuclear/metabolismo , Fragmentos de Peptídeos/metabolismo , Ligação Proteica/fisiologia , Estrutura Terciária de Proteína/fisiologia , Proteínas de Ligação a RNA , Saccharomyces cerevisiae , Fatores de Transcrição/metabolismo , Técnicas do Sistema de Duplo-HíbridoRESUMO
Mutations in the genes encoding the inner nuclear membrane proteins lamin A/C and emerin produce cardiomyopathy and muscular dystrophy in humans and mice. The mechanism by which these broadly expressed gene products result in tissue-specific dysfunction is not known. We have identified a protein of the inner nuclear membrane that is highly expressed in striated and smooth muscle. This protein, myne-1 (myocyte nuclear envelope), is predicted to have seven spectrin repeats, an interrupted LEM domain and a single transmembrane domain at its C-terminus. We found that myne-1 is expressed upon early muscle differentiation in multiple intranuclear foci concomitant with lamin A/C expression. In mature muscle, myne-1 and lamin A/C are perfectly colocalized, although colocalization with emerin is only partial. Moreover, we show that myne-1 and lamin A/C coimmunoprecipitate from differentiated muscle in vitro. The muscle-specific inner nuclear envelope expression of myne-1, along with its interaction with lamin A/C, indicates that this gene is a potential mediator of cardiomyopathy and muscular dystrophy.
