The Actin-Based Motor Myosin Vb Is Crucial to Maintain Epidermal Barrier Integrity

Abstract

Myosin Vb (Myo5b) is an unconventional myosin involved in the actin-dependent transport and tethering of intracellular organelles. In the epidermis, granular keratinocytes accumulate cytoplasmic lamellar bodies (LBs), secretory vesicles released at the junction with the stratum corneum that participate actively in the maintenance of the epidermal barrier. We have previously demonstrated that LB biogenesis is controlled by the Rab11a guanosine triphosphate hydrolase, known for its ability to recruit the Myo5b motor. In order to better characterize the molecular pathway that controls LB trafficking, we analyzed the role of F-actin and Myo5b in the epidermis. We demonstrated that LB distribution in granular keratinocytes was dependent on a dynamic F-actin cytoskeleton. Myo5b was shown to be highly expressed in granular keratinocytes and associated with corneodesmosin-loaded LB. In reconstructed human epidermis, Myo5b silencing led to epidermal barrier defects associated with structural alterations of the stratum corneum and a reduced pool of LB showing signs of disordered maturation. Myo5b depletion also disturbed the expression and distribution of both LB cargoes and junctional components, such as claudin-1, which demonstrates its action on both LB trafficking and junctional complex composition. Together, our data reveal the essential role of Myo5b in maintaining the epidermal barrier integrity.

3D-Organotypic Cultures to Unravel Molecular and Cellular Abnormalities in Atopic Dermatitis and Ichthyosis Vulgaris

“…This is in line with more recent work showing a role for actin-based motor myosin Vb (Myo5b) in maintaining epidermal barrier integrity by controlling LB secretion [53]. Indeed, HEEs silenced for MYO5B displayed epidermal barrier defects associated with structural alterations of the SC and a reduced LB pool, resembling observations made in AD [53]. This work strongly suggests that LB distribution in granular KCs might be dependent on a dynamic F-actin cytoskeleton [53].…”

“…Thus, this work suggests, for the first time, that microtubules are abnormal in the epidermis of AD skin lesions, where they might sustain a dysfunctional epidermal barrier and, in turn, perpetuate the disease [111]. This is in line with more recent work showing a role for actin-based motor myosin Vb (Myo5b) in maintaining epidermal barrier integrity by controlling LB secretion [53]. Indeed, HEEs silenced for MYO5B displayed epidermal barrier defects associated with structural alterations of the SC and a reduced LB pool, resembling observations made in AD [53].…”

“…Indeed, HEEs silenced for MYO5B displayed epidermal barrier defects associated with structural alterations of the SC and a reduced LB pool, resembling observations made in AD [53]. This work strongly suggests that LB distribution in granular KCs might be dependent on a dynamic F-actin cytoskeleton [53].…”

“…This latter phenotype results from disruption of the mature lamellar bilayer organization, owing to incompletely processed lamellar material, aberrant LB internal structures and LB entombment, premature secretion of LB contents into the extracellular spaces of the SG, and inhomogeneous secretion at the SG-SC interface [19,49]. Overall, these studies show that subtle changes in epidermal lipid composition observed in FLG deficiency are sufficient to disorganize SC lipids and alter LB formation, albeit other factors such as the F-actin cytoskeleton might also be involved [53].…”

Safety of oral administration of high doses of ivermectin by means of biocompatible polyelectrolytes formulation

“…In examining the immunofluorescence, we observed an increase in Myosin-Vb staining at apical regions of enterocytes (Figure 2c) indicating that ivermectin resulted in increased expression of the Myosin-Vb at those apical regions. In polarized epithelial cells of intestinal enterocytes [37], the synergistic between Rab11a and the actin-based motor Myosin-Vb plays a crucial role in the regulation of apical trafficking [38], hence Myosin-Vb has an essential role in maintaining the epidermal barrier integrity. The characterized overexpression indicates that Myosin-Vb is affected by the high concentration of ivermectin leading to possible alteration in Myosin-Vb function, which can have implications in the intestinal epidermal integrity.…”