RESUMEN
Biological membranes are composed of a lipid bilayer with embedded proteins, including ion channels like the epithelial sodium channel (ENaC), which are critical for sodium homeostasis and implicated in arterial hypertension (HTN). Changes in the lipid composition of the plasma membrane can significantly impact cellular processes related to physiological functions. We hypothesized that the observed overexpression of ENaC in neutrophils from HTN patients might result from alterations in the structuring domains within the plasma membrane, disrupting the endocytic processes responsible for ENaC retrieval. This study assessed the structural lipid composition of neutrophil plasma membranes from HTN patients along with the expression patterns of key elements regulating ENaC at the plasma membrane. Our findings suggest alterations in microdomain structure and SGK1 kinase activity, which could prolong ENaC presence on the plasma membrane. Additionally, we propose that the proteasomal and lysosomal degradation pathways are insufficient to diminish ENaC presence at the plasma membrane in HTN. These results highlight the importance of understanding ENaC retrieval mechanisms and suggest that targeting these mechanisms could provide insights for developing drugs to prevent and treat HTN.
Asunto(s)
Membrana Celular , Endocitosis , Canales Epiteliales de Sodio , Hipertensión , Neutrófilos , Canales Epiteliales de Sodio/metabolismo , Humanos , Neutrófilos/metabolismo , Hipertensión/metabolismo , Hipertensión/patología , Membrana Celular/metabolismo , Lípidos de la Membrana/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Masculino , Femenino , Proteínas Inmediatas-Precoces/metabolismo , Persona de Mediana Edad , Microdominios de Membrana/metabolismoRESUMEN
In humans, the cytoplasmic FMR1 interacting protein (CYFIP) family is composed of CYFIP1 and CYFIP2. Despite their high similarity and shared interaction with many partners, CYFIP1 and CYFIP2 act at different points in cellular processes. CYFIP1 and CYFIP2 have different expression levels in human tissues, and knockout animals die at different time points of development. CYFIP1, similar to CYFIP2, acts in the WAVE regulatory complex (WRC) and plays a role in actin dynamics through the activation of the Arp2/3 complex and in a posttranscriptional regulatory complex with the fragile X mental retardation protein (FMRP). Previous reports have shown that CYFIP1 and CYFIP2 may play roles in posttranscriptional regulation in different ways. While CYFIP1 is involved in translation initiation via the 5'UTR, CYFIP2 may regulate mRNA expression via the 3'UTR. In addition, this CYFIP protein family is involved in neural development and maturation as well as in different neural disorders, such as intellectual disabilities, autistic spectrum disorders, and Alzheimer's disease. In this review, we map diverse studies regarding the functions, regulation, and implications of CYFIP proteins in a series of molecular pathways. We also highlight mutations and their structural effects both in functional studies and in neural diseases.