The spectrin cytoskeleton is a major component of the mammalian cell cortex. While long known and ubiquitously expressed, its dynamic behaviour and cooperation with other major components of the cell cortex is poorly understood. Here we investigated spectrin reactions upon different mechanical cues, such as cell-driven perturbations, like cell adhesion, spreading and contraction, or environmentally driven ones, like compression, stretch and osmotic changes. Upon all of these challenges we observed that spectrin meshwork spatially adapts and reorganizes under the plasma membrane together with the acto-myosin cytoskeleton. Working together to maintain cell integrity, both cytoskeletons define specific membrane territories. Actin-rich regions control protrusions, adhesions and stress fibers, whereas spectrin-rich regions concentrate in retractile zones, covering low actin density territories of the cortex. Given this interplay, we wondered if spectrin could be potentially involved in the spatial and temporal regulation of membrane trafficking. We followed spectrin, actin and clathrin dynamics through live TIRF microscopy and observed an inverted correlation between spectrin and actin densities and endocytic capacities, suggesting a spectrin contribution to clathrin-mediated endocytosis. Our results pinpoint a role for spectrin in the support of the lipid bilayer in regions where actin cytoskeleton is not established, creating a fencing mechanism for actin remodelling and cargoes internalization. All these mechanisms potentially unveil why the spectrin family of protein is evolutionary highly conserved and ubiquitously expressed in eukaryotic cells, and might explain its involvement in a broad range of pathological condition.
|Titolo:||DYNAMIC INTERPLAY BETWEEN SPECTRIN, ACTIN AND PLASMA MEMBRANE DURING CELL MECHANORESPONSE|
|Data di pubblicazione:||28-gen-2020|
|Parole Chiave:||Mechanobiology; plasma membrane; microscopy|
|Settore Scientifico Disciplinare:||Settore BIO/10 - Biochimica|
|Citazione:||DYNAMIC INTERPLAY BETWEEN SPECTRIN, ACTIN AND PLASMA MEMBRANE DURING CELL MECHANORESPONSE / C. Galli ; supervisor: N. Gauthier. - Milano : Università degli studi di Milano. DIPARTIMENTO DI ONCOLOGIA ED EMATO-ONCOLOGIA, 2020 Jan 28. ((31. ciclo, Anno Accademico 2019.|
|Appare nelle tipologie:||Tesi di dottorato|