Espins and the actin cytoskeleton of hair cell stereocilia and sensory cell microvilli

Abstract

The espins are novel actin-bundling proteins that are produced in multiple isoforms from a single gene. They are present at high concentration in the parallel actin bundle of hair cell stereocilia and are the target of deafness mutations in mice and humans. Espins are also enriched in the microvilli of taste receptor cells, solitary chemoreceptor cells, vomeronasal sensory neurons and Merkel cells, suggesting that espins play important roles in the microvillar projections of vertebrate sensory cells. Espins are potent actin-bundling proteins that are not inhibited by Ca 2+ . In cells, they efficiently elongate parallel actin bundles and, thereby, help determine the steady-state length of microvilli and stereocilia. Espins bind actin monomer via their WH2 domain and can assemble actin bundles in cells. Certain espin isoforms can also bind phosphatidylinositol 4,5-bisphosphate, profilins or SH3 proteins. These biological activities distinguish espins from other actin-bundling proteins and may make them well-suited to sensory cells. KeywordsEspin; actin; hair cell; stereocilia; microvilli; sensory; deafness; taste The stereocilia and microvilli of vertebrate sensory cells and their actinbundling proteinsMany classes of vertebrate sensory cells detect chemical or mechanical stimuli through microvilli or their derivatives, such as stereocilia. These relatively long-lived, fingerlike specializations of the plasma membrane are built around a common cytoskeletal element -the parallel actin bundle (PAB) [1]. PABs consist of tightly packed collections of actin filaments cross-linked by actin-bundling proteins. The filaments are aligned along their longitudinal axis and display a uniform polarity with respect to their preferred ends for actin monomer addition, which in microvilli and stereocilia is positioned at the distal tip. The PAB displays hallmarks of a supramolecular scaffold that determines the placement, dimensions, flexibility and signaling properties of microvilli and stereocilia. Although filopodia also contain a PAB at their core and are believed to sense the local environment, they are considerably more dynamic and differ significantly from microvilli and stereocilia in their molecular composition and biogenesis [2].

Control of Actin Assembly Dynamics in Cell Motility

“…The actin filament has a versatile structure, and subtle structural changes induced by barbed end-binding regulators may favor the binding of, for example, distinctive bundling proteins, thus further differentiating the function of actin arrays. This might explain why bundling proteins like fascin (37) or espin (38) are found associated with bundles of filaments initiated by different machineries.…”

Actin-Binding Protein, Espin: A Novel Metastatic Regulator for Melanoma

“…S1; refs. 4,5). All isoforms of ESPIN encode the same region of a 116-amino acid actin-bundling module (ABM), which is necessary for potent actin-bundling and microvillar parallel actin bundle (PAB) elongating activities (4,5).…”

“…4,5). All isoforms of ESPIN encode the same region of a 116-amino acid actin-bundling module (ABM), which is necessary for potent actin-bundling and microvillar parallel actin bundle (PAB) elongating activities (4,5). Mutation in Wiskott-Aldrich syndrome protein homology 2 (WH2) and ABM domains of ESPIN gene causes hereditary deafness and vestibular dysfunction accompanied by stereociliary shortening in jerker mice and humans (5,6).…”

“…All isoforms of ESPIN encode the same region of a 116-amino acid actin-bundling module (ABM), which is necessary for potent actin-bundling and microvillar parallel actin bundle (PAB) elongating activities (4,5). Mutation in Wiskott-Aldrich syndrome protein homology 2 (WH2) and ABM domains of ESPIN gene causes hereditary deafness and vestibular dysfunction accompanied by stereociliary shortening in jerker mice and humans (5,6). Espins are also capable of affecting the actin cytoskeleton, resulting in a special connection to microvillar specializations of sensory cells such as taste receptor cells, solitary chemoreceptor cells, and Merkel cells (7).…”

Myosin VIIA regulates microvillus morphogenesis and interacts with cadherin Cad99C in Drosophila oogenesis

“…A number of factors have been identified that contribute to the length regulation of microvilli or microvillusderived stereocilia and their organization and arrangement on the apical surface of epithelial cells. Many of these factors directly bind to actin in protrusions, either cross-linking actin filaments or linking them to the plasma membrane (reviewed by Lin et al, 2005;Sekerková et al, 2006;Manor and Kachar, 2008;Tepass, 2009;Fehon et al, 2010). In particular, myosin motor proteins, which bind to and travel along actin filaments, control multiple processes in microvilli and stereocilia.…”