RESUMO
During development, lymphatic endothelial cell (LEC) progenitors differentiate from venous endothelial cells only in limited regions of the body. Thus, LEC migration and subsequent tube formation are essential processes for the development of tubular lymphatic vascular network throughout the body. In this review, we discuss chemotactic factors, LEC-extracellular matrix interactions and planar cell polarity regulating LEC migration and formation of tubular lymphatic vessels. Insights into molecular mechanisms underlying these processes will help in understanding not only physiological lymphatic vascular development but lymphangiogenesis associated with pathological conditions such as tumors and inflammation.
RESUMO
Constriction of the apical plasma membrane is a hallmark of epithelial cells that underlies cell shape changes in tissue morphogenesis and maintenance of tissue integrity in homeostasis. Contractile force is exerted by a cortical actomyosin network that is anchored to the plasma membrane by the apical junctional complexes (AJC). In this study, we present evidence that MAGI proteins, structural components of AJC whose function remained unclear, regulate apical constriction of epithelial cells through the Par polarity proteins. We reveal that MAGIs are required to uniformly distribute Partitioning defective-3 (Par-3) at AJC of cells throughout the epithelial monolayer. MAGIs recruit ankyrin-repeat-, SH3-domain- and proline-rich-region-containing protein 2 (ASPP2) to AJC, which modulates Par-3-aPKC to antagonize ROCK-driven contractility. By coupling the adhesion machinery to the polarity proteins to regulate cellular contractility, we propose that MAGIs play essential and central roles in maintaining steady state intercellular tension throughout the epithelial cell sheet.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Moléculas de Adesão Celular/metabolismo , Polaridade Celular , Forma Celular , Células Epiteliais/enzimologia , Guanilato Quinases/metabolismo , Junções Intercelulares/enzimologia , Proteína Quinase C/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Moléculas de Adesão Celular/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Guanilato Quinases/genética , Células HEK293 , Homeostase , Humanos , Junções Intercelulares/genética , Transdução de Sinais , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Proteína da Zônula de Oclusão-1/genética , Proteína da Zônula de Oclusão-1/metabolismo , Proteína da Zônula de Oclusão-2/genética , Proteína da Zônula de Oclusão-2/metabolismo , Quinases Associadas a rho/metabolismoRESUMO
Neuropeptide Y (NPY) and its receptors affect blood pressure, feeding behavior, and neurogenesis. In this study, the distribution of neurons expressing NPY Y5 receptor (Y5) was examined in adult mouse central nervous system by immunohistochemistry. Y5 protein localization was investigated using polyclonal anti-Y5 antibody, which was successfully preabsorbed with Y5 knockout brain tissues. The preabsorbed anti-Y5 antibody did not react with Y5 knockout brain tissues, thus meeting the "hard specificity criterion," which is the absence of staining in tissues genetically deficient for the antigen (Pradidarcheep et al., 2008). Y5-positive neurons were found in most brain areas. Most Y5 immunoreactivities were observed as dot-like structures adjacent to the plasma membrane, as expected for a cell membrane receptor. In situ hybridization showed that the Y5 mRNA expression was correlated with the Y5 protein level in each case and that it was probably controlled by the transcriptional regulation of the Y5 gene. In the nuclei where Y5 was expressed, Y5 immunoreactivities were found mainly in the somatic and dendritic areas. The distribution patterns of the Y5-positive cells that were broader than previously expected suggest important biological activities of the Y5 in many brain areas.
Assuntos
Encéfalo/metabolismo , Receptores de Neuropeptídeo Y/metabolismo , Animais , Imunofluorescência , Glutamato Descarboxilase/metabolismo , Hibridização In Situ , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Moléculas de Adesão de Célula Nervosa/metabolismo , Neurônios/metabolismo , RNA Mensageiro/metabolismo , Receptores de Neuropeptídeo Y/genéticaRESUMO
Neuropeptide Y (NPY) is a potent neurotransmitter for feeding. Besides NPY, orexigenic neuropeptides such as agouti-related protein (AgRP), and anorexigenic neuropeptides such as alpha-melatonin stimulating hormone (MSH) and cocaine-amphetamine-regulated transcript (CART) are also involved in central feeding regulation. During fasting, NPY and AgRP gene expressions are up-regulated and POMC and CART gene expressions are down-regulated in hypothalamus. Based on the network of peptidergic neurons, the former are involved in positive feeding regulation, and the latter are involved in negative feeding, which exert these feeding-regulated peptides especially in paraventricular nucleus (PVN). To clarify the compensatory mechanism of knock-out of NPY system on feeding, change in gene expressions of appetite-related neuropeptides and the feeding behavior was studied in NPY Y5-KO mice. Food intake was increased in Y5-KO mice. Fasting increased the amounts of food and water intake in the KO mice more profoundly. These data indicated the compensatory phenomenon of feeding behavior in Y5-KO mice. RT-PCR and ISH suggested that the compensation of feeding is due to change in gene expressions of AgRP, CART and POMC in hypothalamus. Thus, these findings indicated that the compensatory mechanism involves change in POMC/CART gene expression in arcuate nucleus (ARC). The POMC/CART gene expression is important for central compensatory regulation in feeding behavior.
