RESUMO
The microscopic environment inside a metazoan organism is highly crowded. Whether individual cells can tailor their behavior to the limited space remains unclear. In this study, we found that cells measure the degree of spatial confinement by using their largest and stiffest organelle, the nucleus. Cell confinement below a resting nucleus size deforms the nucleus, which expands and stretches its envelope. This activates signaling to the actomyosin cortex via nuclear envelope stretch-sensitive proteins, up-regulating cell contractility. We established that the tailored contractile response constitutes a nuclear ruler-based signaling pathway involved in migratory cell behaviors. Cells rely on the nuclear ruler to modulate the motive force that enables their passage through restrictive pores in complex three-dimensional environments, a process relevant to cancer cell invasion, immune responses, and embryonic development.
Assuntos
Mecanotransdução Celular , Membrana Nuclear/fisiologia , Actomiosina/metabolismo , Animais , Movimento Celular , Desenvolvimento Embrionário , Células HeLa , Humanos , Camundongos , Cadeias Pesadas de Miosina/metabolismo , Invasividade Neoplásica , Neoplasias/patologiaRESUMO
Membrane microdomains (lipid rafts) are enriched in selected signaling molecules and may compartmentalize receptor-mediated signals. Here, we report that in primary human B lymphocytes and in Ramos B cells B cell receptor (BCR) stimulation induces rapid and transient redistribution of a subset of engaged BCRs to lipid rafts and phosphorylation of raft-associated tyrosine kinase substrates. Cholesterol sequestration disrupted the lipid rafts, preventing BCR redistribution, but did not inhibit tyrosine kinase activation or phosphorylation of mitogen-activated protein kinase/extracellular regulated kinase. However, raft disruption enhanced the release of calcium from intracellular stores, suggesting that rafts may sequester early signaling events that down-regulate calcium flux. Consistent with this, BCR stimulation induced rapid and transient translocation of the Src homology 2 domain-containing inositol phosphatase, SHIP, into lipid rafts.
Assuntos
Linfócitos B/metabolismo , Sinalização do Cálcio/imunologia , Lipídeos de Membrana/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Receptores de Antígenos de Linfócitos B/metabolismo , Domínios de Homologia de src/imunologia , Linfócitos B/enzimologia , Transporte Biológico/imunologia , Cálcio/metabolismo , Criança , Humanos , Líquido Intracelular/metabolismo , Lipídeos de Membrana/isolamento & purificação , Tonsila Palatina , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases , Fosforilação , Proteínas Tirosina Quinases/metabolismo , Receptores de Antígenos de Linfócitos B/fisiologia , Especificidade por Substrato/imunologia , Células Tumorais CultivadasRESUMO
Two Quarter Horse foals from different premises died from enterotoxemia. Clostridium perfringens toxins alpha and beta were demonstrated in the foal's intestines by mouse protection tests. Clostridium perfringens type C was isolated from the intestines of each foal. Histologic examination revealed hemorrhage, necrosis, and massive numbers of C perfringens.
