RESUMEN
The small G-protein CDC42 is an evolutionary conserved polarity protein and a key regulator of polarized cell functions, including directed cell migration. In vertebrates, alternative splicing gives rise to two CDC42 proteins: the ubiquitously expressed isoform (CDC42u) and the brain isoform (CDC42b), which only differ in their carboxy-terminal sequence, including the CAAX motif essential for their association with membranes. We show that these divergent sequences do not directly affect the range of CDC42's potential binding partners but indirectly influence CDC42-driven signaling by controlling the subcellular localization of the two isoforms. In astrocytes and neural precursors, which naturally express both variants, CDC42u associates with the leading-edge plasma membrane of migrating cells, where it recruits the Par6-PKCζ complex to fulfill its polarity function. In contrast, CDC42b mainly localizes to intracellular membrane compartments, where it regulates N-WASP-mediated endocytosis. Both CDC42 isoforms contribute their specific functions to promote the chemotaxis of neural precursors, demonstrating that their expression pattern is decisive for tissue-specific cell behavior.
Asunto(s)
Empalme Alternativo , Astrocitos , Movimiento Celular , Proteína de Unión al GTP cdc42 , Animales , Astrocitos/citología , Isoformas de Proteínas/genética , Ratas , Proteína de Unión al GTP cdc42/genética , Membrana CelularAsunto(s)
Enfermedades Autoinmunes/genética , Dermatitis Exfoliativa/genética , Inflamación/genética , Mutación/genética , FN-kappa B/metabolismo , Psoriasis/genética , Proteína de Unión al GTP cdc42/metabolismo , Actinas/metabolismo , Inhibidores de Disociación de Guanina Nucleótido/metabolismo , Humanos , Lactante , Lipoilación , Masculino , Linaje , Unión Proteica , Transducción de Señal , Síndrome , Secuenciación del Exoma , Proteína de Unión al GTP cdc42/genéticaRESUMEN
Membrane trafficking plays a crucial role in cell polarity by directing lipids and proteins to specific subcellular locations in the cell and sustaining a polarized state. The Golgi apparatus, the master organizer of membrane trafficking, can be subdivided into three layers that play different mechanical roles: a cytoskeletal layer, the so-called Golgi matrix, and the Golgi membranes. First, the outer regions of the Golgi apparatus interact with cytoskeletal elements, mainly actin and microtubules, which shape, position, and orient the organelle. Closer to the Golgi membranes, a matrix of long coiled-coiled proteins not only selectively captures transport intermediates but also participates in signaling events during polarization of membrane trafficking. Finally, the Golgi membranes themselves serve as active signaling platforms during cell polarity events. We review here the recent findings that link the Golgi apparatus to cell polarity, focusing on the roles of the cytoskeleton, the Golgi matrix, and the Golgi membranes.
