RESUMEN
Asymmetric cell division generates cell fate diversity during development and adult life. Recent findings have demonstrated that during stem cell divisions, the movement of centrosomes is asymmetric in prophase and that such asymmetry participates in mitotic spindle orientation and cell polarization. Here, we have investigated the dynamics of centrosomes during Drosophila sensory organ precursor asymmetric divisions and find that centrosome movements are asymmetric during cytokinesis. We demonstrate that centrosome movements are controlled by the cell fate determinant Numb, which does not act via its classical effectors, Sanpodo and α-Adaptin, but via the Collapsin Response Mediator Protein (CRMP). Furthermore, we find that CRMP is necessary for efficient Notch signalling and that it regulates the duration of the pericentriolar accumulation of Rab11-positive endosomes, through which the Notch ligand, Delta is recycled. Our work characterizes an additional mode of asymmetric centrosome movement during asymmetric divisions and suggests a model whereby the asymmetry in centrosome movements participates in differential Notch activation to regulate cell fate specification.
Asunto(s)
Centrosoma/metabolismo , Proteínas de Drosophila/metabolismo , Hormonas Juveniles/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Órganos de los Sentidos/citología , Células Madre/citología , Células Madre/metabolismo , Animales , Diferenciación Celular/genética , Diferenciación Celular/fisiología , Drosophila , Proteínas de Drosophila/genética , Inmunoprecipitación , Hormonas Juveniles/genética , Proteínas del Tejido Nervioso/genéticaRESUMEN
When you look at the dorsal thorax of a fruitfly, you can easily get fascinated by the high degree of alignment of the bristles that show a strong polarization in their surface organization. This organization of cells in the plane of the epithelium is known as planar cell polarity (PCP), and was initially characterized in Drosophila melanogaster. This process is important in a broad variety of morphological cellular asymmetries in various organisms. In Drosophila, genetic studies of PCP mutants showed that the asymmetric division of the sensory organ precursor cell (pI cell) is polarized along the anterior-posterior axis by Frizzled receptor signaling. Here, we described two methods to image and analyze the PCP in the pI cell model.
Asunto(s)
División Celular , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/citología , Receptores Frizzled/metabolismo , Imagen Molecular/métodos , Transducción de Señal , Fijación del Tejido/métodos , Animales , Disección , Inmunohistoquímica , Pupa/citología , Factores de TiempoRESUMEN
Engagement of the B cell receptor (BCR) by surface-tethered antigens (Ag) leads to formation of a synapse that promotes Ag uptake for presentation onto major histocompatibility complex class II (MHCII) molecules. We have highlighted the membrane trafficking events and associated molecular mechanisms involved in Ag extraction and processing at the B cell synapse. MHCII-containing lysosomes are recruited to the synapse where they locally undergo exocytosis, allowing synapse acidification and the extracellular release of hydrolases that promote the extraction of the immobilized Ag. Lysosome recruitment and secretion results from the polarization of the microtubule-organizing center (MTOC), which relies on the cell division cycle (Cdc42)-downstream effector, atypical protein kinase C (aPKCζ). aPKCζ is phosphorylated upon BCR engagement, associates to lysosomal vesicles, and is required for their polarized secretion at the B cell synapse. Regulation of B lymphocyte polarity therefore emerges as a central mechanism that couples Ag extraction to Ag processing and presentation.
