Dynamic actin-mediated nano-scale clustering of CD44 regulates its meso-scale organization at the plasma membrane

Abstract

We show a hierarchical organization of the adhesion receptor CD44 at multiple-length scales on the plasma membrane by studying the diffusion and clustering behavior of the protein.

Formin nanoclustering-mediated actin assembly during plant flagellin and DSF signaling

“…Integration of type-I formin within the multilayer tensegrity structure, CW-PM-AC continuum (Figure 6), controls the condensation and biochemical activities of formin and the architecture of cortical actin networks. By connecting with the PM by pinning sites, type-I formin might serve as mobile poles in a picket-fence actin meshwork, similar to the model that was proposed in the mammalian system (Figure 6) (Gowrishankar et al, 2012;Saha et al, 2015;Sil et al, 2020). Inter-linked cellular skeleton structures influence lateral mobility on the PM in mammalian cells.…”

“…Together, the in vivo and in vitro results suggest that the higher-order clustering of formin might not be derived from the direct multivalent forminformin interactions, and additional unknown factors might be involved in recruiting and clustering formins to form nanoclusters and large punctae in vivo. It is conceivable that formin-based actin polymerization-driven nanoscale clustering, as observed for CD44 (Sil et al, 2020), may serve as a model for how the membrane-attached formin organizes itself into nanoclusters.…”

“…For example, the integrin nanoclustering is critical for its function in cell adhesion, which requires the mechanical properties of the extracellular matrix (ECM), glycosylphosphatidylinositol-anchored proteins (GPI-APs) at the extracellular leaflet of PM, and actin cytoskeleton coupling to inner-leaflet lipids (Kalappurakkal et al, 2019;Paszek et al, 2009). Plant type-I formin has similar features of mammalian integrins or transmembrane adhesion receptors (Kalappurakkal et al, 2019;Sil et al, 2020) regarding its physical connections toward the extracellular polysaccharide structure and intracellular actin activation. However, by having high motility and nucleation activities, the uniformly distributed type-I formins possess unique associations with the assembled CW/ECM-PM-AC continuum, which influence the dynamics of PM-bound proteins, including type-I formins (Lampugnani et al, 2018;Martiniè re et al, 2012).…”

Proteolytic Processing of CD44 and Its Implications in Cancer

“…CD44 is a cell surface adhesion molecule involved in cell-cell interactions, cell adhesion, and migration [ 1 ]. The main ligand of CD44 is hyaluronic acid (HA), a polysaccharide abundantly present in the extracellular matrix of mammals, yet it can bind to other components of the extracellular matrix and perform different functions depending on the structure of the protein it binds to [ 2 , 3 ]. It is composed of a distal extracellular amino-terminal domain (ECD), a stem region, a transmembrane domain (TM), and an intracellular cytoplasmic carboxy-terminal domain (ICD) ( Figure 1 ).…”

Impact of Glycans on Lipid Membrane Dynamics at the Nanoscale Unveiled by Planar Plasmonic Nanogap Antennas and Atomic Force Spectroscopy

“…Using super-resolution microscopy and/or single-molecule imaging, we and others have revealed that glycans can modulate the degree of clustering, mobility, and/or molecular interactions of different membrane receptors, thereby regulating their function. 9 − 12 …”