Regulation of actin-based apical structures on epithelial cells

Abstract

Cells of transporting epithelia are characterized by the presence of abundant F-actin-based microvilli on their apical surfaces. Likewise, auditory hair cells have highly reproducible rows of apical stereocilia (giant microvilli) that convert mechanical sound into an electrical signal. Analysis of mutations in deaf patients has highlighted the critical components of tip links between stereocilia, and related structures that contribute to the organization of microvilli on epithelial cells have been found. Ezrin/radixin/moesin (ERM) proteins, which are activated by phosphorylation, provide a critical link between the plasma membrane and underlying actin cytoskeleton in surface structures. Here, we outline recent insights into how microvilli and stereocilia are built, and the roles of tip links. Furthermore, we highlight how ezrin is locally regulated by phosphorylation, and that this is necessary to maintain polarity. Localized phosphorylation is achieved through an intricate coincidence detection mechanism that requires the membrane lipid phosphatidylinositol 4,5-bisphosphate [PI(4,5)P 2 ] and the apically localized ezrin kinase, lymphocyteoriented kinase (LOK, also known as STK10) or Ste20-like kinase (SLK). We also discuss how ezrin-binding scaffolding proteins regulate microvilli and how, despite these significant advances, it remains to be discovered how the cell polarity program ultimately interfaces with these processes.

Ultrastructural defects in stereocilia and tectorial membrane in aging mouse and human cochleae

“…Thus, while the increase in width in fused and giant, elongated stereocilia that subsequently develop is likely a result of accumulation of the existing filaments into the fusing stereocilia, the increase in length is presumably due to growth of the actin filaments. Stereocilia grow in length during development by addition of actin monomers to the apical tips of the filaments and are maintained during life by a slow turnover of actin in a small compartment at that tip (Drummond et al, ; McGrath, Roy, & Perrin, ; Narayanan et al, ; Pelaseyed & Bretscher, ). The elongation of stereocilia therefore suggests that the machinery for trafficking actin to the tips of stereocilia is still active, providing additional evidence for the “viability” of the hair cells upon which fused and elongated stereocilia are present.…”

Analysis of eEF1Bγ interactome in the nuclear fraction of A549 human lung adenocarcinoma cells

“…The group comprises EZR and HNRNPH1 (Cytoscape) and CD2AP (MapoftheCell). It is widely accepted that ezrin participates in anchoring membrane proteins to the cortical actin network [118]. Nuclear localization of ezrin was also reported, however, the role of nuclear ezrin is not yet deciphered [119].…”

High‐resolution imaging of the actin cytoskeleton and epithelial sodium channel, CFTR, and aquaporin‐9 localization in the vas deferens

“…Both the microvilli and the much longer stereocilia have backbones that are composed of bundles of actin filaments (Brown & McKnight, 2010; Pelaseyed & Bretscher, 2018). The actin filaments are tethered to the cell membrane by actin‐binding proteins.…”

“…Histological studies have shown that the apical borders of the epithelial cells in the vas deferens are covered by microvilli or stereocilia (Francavilla et al, 1987; Hamilton & Cooper, 1978; Höfer & Drenckhahn, 1996; Rodriguez & Bustos‐Obregón, 1993). Both microvilli and stereocilia are cell projections that have backbones composed of actin filament bundles (Pelaseyed & Bretscher, 2018). In epithelial cells, a network of actin filaments lies underneath the membrane providing structural support for the membrane.…”