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Junction-dependent keratin network organization

Marcin Moch

Desmosomal and hemidesmosomal adhesions together with their associated keratin intermediate filaments are hallmarks of epithelial differentiation with profound contributions to epithelial mechanics and function. Crosstalk between desmosomes and keratin filaments determines epithelial plasticity in different functional contexts. We have recently shown that nascent desmosomes and hemidesmosomes serve as nucleation sites for elongating keratin filaments. Subsequent keratin filament bundling and junctional fusion are coordinated generating a stable transcellular keratin scaffold that is connected to the extracellular matrix and is arranged in a "rim-and-spoke" fashion consisting of interjunctional cortical keratin filament bundles (rim) and radial keratin filament bundles connecting desmosomes with the perinuclear keratin cage (spokes; see Figure 1). Our observations further suggest that the morphogenesis and maintenance of the keratin-desmosome scaffold is guided by the actin cytoskeleton. We are currently investigating this relationship with a focus on the subplasmalemmal keratin-enforced actin-rich cell cortex as a major mechanical component of epithelial cells with potential functions in mechanosensing.

 

Figure 1. Schematic illustration of the spoke-and-rim arrangement of intermediate filaments. The cartoon depicts how radial and cortical keratin filaments connect the desmosomal cell-cell junctions (circumferential rim) and radial spokes the desmosomes to the nucleus. Together they form an adaptable tension-spoke network that is important for maintaining mechanical equilibrium and sensing force changes at the plasma membrane, and transducing these to the nuclear compartment through a direct physical connection mediated by intermediate filaments. (The figure is modified from Quinlan et al, 2017, J Cell Sci 130:3437.)

 

450_9 HaCaT 5 days PFA
Test: ICC PFA Keratin Integrin-beta4