Membrane tension regulates syndecan-1 expression through actin remodelling

Abstract

The endothelial glycocalyx, located at the interface of vascular lumen, is a carbohydrate-rich complex that controls vascular functions such as solute permeation, neutrophil extravasation and mechanotransduction. It anchors to the cell membrane through core proteins, e.g. syndecan-1, which couple to the actin cytoskeleton. Membrane tension plays an important role in the reorganisation of membrane-bound proteins, however, little is known on the effect of the membrane tension on the various components of the glycocalyx. In the current study, we use hypo-osmotic stress to investigate the effect of the membrane tension on syndecan-1 expression.Our results show that following 20 min exposure to hypo-osmotic medium, the expression of syndecan-1 in the endothelial glycocalyx layer is reduced to 84.7 ± 3.6 % (255 mOsm) and 64.7 ± 2.1 % (167 mOsm). This reduction, however, is transient and partial recovery is observed at the end of 2 h exposure to the hypo-osmotic medium. The transient reduction of syndecan-1 is associated with depolymerisation of the actin cytoskeleton. Further examination of the effect of actin manipulation reveals that actin depolymerisation by cytochalasin D results in sustained syndecan-1 reduction. In contrast, stabilising actin using jasplakinolide abolishes the transient reduction of syndecan-1completely. Taken together, we demonstrate, for the first time, that membrane tension plays an important role in the regulation of syndecan-1 expression and this effect is mediated by the reorganisation of the actin cytoskeleton. Findings in this study suggest a new venue of research on the protective role of the glycocalyx in vascular pathophysiology and diseases.

A Reinterpretation of Evidence for the Endothelial Glycocalyx Filtration Structure

“…The second is that a change of lattice structure, for example to a SQ core formation, would radically alter the reflection coefficient to albumin and indeed the permeability to macromolecules. Whilst speculative in the context here, this type of formational change is feasible, for example by selective binding mechanisms to the actin cytoskeleton ( Yoneda and Couchman, 2003 ; Multhaupt et al, 2009 ; Li and Wang, 2019 ), and would allow for great functional control over what is a dynamic system. Further, there would still be direct GAG control over the filtration via other mechanisms, such as those hypothesized in immunology for clumping of the HS leaving short term gaps ( Dyer et al, 2017 ; Handel and Dyer, 2021 ) as well as the activity of shedases [e.g., ( Annecke et al, 2011 )].…”

Endomucin regulates the endothelial cytoskeleton independent of VEGF

“…The actin cytoskeleton governs multiple cellular functions, and rapid remodeling of the endothelium is required for cell adhesion and migration [28,29]. The glycocalyx is believed to be anchored to the actin cytoskeleton via core proteins such as syndecans, an interaction has been implicated in mechanosensation and transduction [30][31][32]. The mechanism by which the glycocalyx communicates changes to the cytoskeleton is less understood.…”

Biomechanical properties of endothelial glycocalyx: An imperfect pendulum

“…While cytochalasin B or D and jasplakinolide by halting or increasing actin polymerization, respectively, result in changes in the height of EG and shedding of EG leads to the loss of reorganization of the cortical actin web [24] and with it, in turn, the loss of shear stress-induced reorganization of cortical actin web. Hypoosmotic ambient stress temporarily reduces the expression of syndecan-1 in the endothelial glycocalyx, pari passu with depolymerization of F-actin cortical web [11] , which partially recovers within 2 h in parallel with the reconstitution of syndecan-1. Permanent depolymerizing action of cytochalasin D, however, leads to the sustained downregulation of syndecan-1, whereas stabilization of F-actin by application of jasplakinolide prevents hypoosmotic stress-induced decline in syndecan-1.…”

“…In the equation, T is the apparent membrane tension, T m in-plane membrane tension γ surface tension, k the elastic modulus and A cell surface area] determines cell shape, the activity of exo- and endo-cytotic processes, as well as the transitions between plain and lipid-rich domains [10] . Among this multitude of functions, membrane tension as manipulated, for instance, by exposing endothelial cells to various ambient osmolarity, has been reported to regulate syndecan-1 expression via remodeling of the cortical actin cytoskeleton [11] . In turn, cortical actin is itself in the state of constant remodeling through polymerization-depolymerization.…”