Assuntos
Eliptocitose Hereditária/cirurgia , Esplenectomia/métodos , Transfusão de Sangue , Terapia Combinada , Eliptocitose Hereditária/sangue , Eliptocitose Hereditária/fisiopatologia , Ferritinas/sangue , Seguimentos , Hemoglobinas/análise , Humanos , Lactente , Tamanho do Órgão , Contagem de Plaquetas , Reoperação , Estudos Retrospectivos , Baço/fisiopatologia , Resultado do TratamentoRESUMO
The classical function of 4.1R in red blood cells is to contribute to the mechanochemical properties of the membrane by promoting the interaction between spectrin and actin. More recently, it has been recognized that 4.1R is required for the stable cell surface accumulation of a number of erythrocyte membrane proteins. 4.1R is one member of the mammalian 4.1 family - the others being 4.1N, 4.1G and 4.1B - and is expressed in many cell types other than erythrocytes. Recently we have examined the phenotype of hearts from 4.1R knockout mice. Although they had a generally normal morphology, these hearts exhibited bradycardia, and prolongation of both action potentials and QT intervals. Electrophysiological analysis revealed anomalies in a range of ion channel activities. In addition, the immunoreactivity of voltage-gated Na(+) channel NaV1.5 was reduced, indicating a role for 4.1R in the cellular accumulation of this ion channel. 4.1 proteins also have roles in the accumulation of at least two other classes of ion channel. In epithelia, 4.1 interacts with the store-operated channel TRPC4. In neurons, the ligand-gated channels GluR1 and GluR4 require 4.1 proteins for cell surface accumulation. The spectrum of transmembrane proteins that bind to 4.1 proteins overlaps with that of ankyrin. A hypothesis to investigate in the future is that differential regulation of 4.1 and ankyrins (e.g. by PIP(2)) allows highly selective control of cell surface accumulation and transport activity of a specific range of ion channels.
Assuntos
Proteínas Sanguíneas/fisiologia , Proteínas do Citoesqueleto/fisiologia , Canais Iônicos/fisiologia , Proteínas de Membrana/fisiologia , Animais , Arritmias Cardíacas/genética , Proteínas Sanguíneas/química , Proteínas Sanguíneas/deficiência , Proteínas Sanguíneas/genética , Proteínas Sanguíneas/metabolismo , Bradicardia/genética , Bradicardia/fisiopatologia , Proteínas do Citoesqueleto/química , Proteínas do Citoesqueleto/genética , Eliptocitose Hereditária/sangue , Eliptocitose Hereditária/genética , Eliptocitose Hereditária/fisiopatologia , Células Epiteliais/metabolismo , Eritrócitos/metabolismo , Coração/fisiopatologia , Humanos , Síndrome do QT Longo/genética , Síndrome do QT Longo/fisiopatologia , Proteínas de Membrana/química , Proteínas de Membrana/genética , Camundongos , Proteínas dos Microfilamentos , Família Multigênica , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Canal de Sódio Disparado por Voltagem NAV1.5 , Neurônios/metabolismo , Estrutura Terciária de Proteína , Canais de Sódio/metabolismoRESUMO
A number of proteins that make up the membrane skeleton have been identified, and we have a rough but tantalizing picture of the ways in which they interact to maintain its integrity. An approximate molecular model of spectrin has been proposed, and many new analytic procedures have been developed to search for biochemical variants that may be related to membrane defects. Even at this rudimentary stage of molecular description we have been able to identify structural changes in spectrin that are correlated with pathophysiologic states. The prospects for some genuine insights into the pathogenesis of some congenital hemolytic anemias seem good.