title: Espins are multifunctional actin cytoskeletal regulatory proteins in the microvilli of chemosensory and mechanosensory cells.
abstract: Espins are associated with the parallel actin bundles of hair cell stereocilia and are the target of mutations that cause deafness and vestibular dysfunction in mice and humans. Here, we report that espins are also concentrated in the microvilli of a number of other sensory cells: vomeronasal organ sensory neurons, solitary chemoreceptor cells, taste cells, and Merkel cells. Moreover, we show that hair cells and these other sensory cells contain novel espin isoforms that arise from a different transcriptional start site and differ significantly from other espin isoforms in their complement of ligand-binding activities and their effects on actin polymerization. The novel espin isoforms of sensory cells bundled actin filaments with high affinity in a Ca(2+)-resistant manner, bound actin monomer via a WASP (Wiskott-Aldrich syndrome protein) homology 2 domain, bound profilin via a single proline-rich peptide, and caused a dramatic elongation of microvillus-type parallel actin bundles in transfected epithelial cells. In addition, the novel espin isoforms of sensory cells differed from other espin isoforms in that they potently inhibited actin polymerization in vitro, did not bind the Src homology 3 domain of the adapter protein insulin receptor substrate p53, and did not bind the acidic, signaling phospholipid phosphatidylinositol 4,5-bisphosphate. Thus, the espins constitute a family of multifunctional actin cytoskeletal regulatory proteins with the potential to differentially influence the organization, dimensions, dynamics, and signaling capabilities of the actin filament-rich, microvillus-type specializations that mediate sensory transduction in various mechanosensory and chemosensory cells.
authors.affiliation: Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Sekerková
authors.forename: Lili
authors.initials: L
authors.lastname: Zheng
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Loomis
authors.forename: Benjarat
authors.initials: B
authors.lastname: Changyaleket
authors.forename: Donna S
authors.initials: DS
authors.lastname: Whitlon
authors.forename: Enrico
authors.initials: E
authors.lastname: Mugnaini
authors.forename: James R
authors.initials: JR
authors.lastname: Bartles
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002628:Chemoreceptor Cells / Q000737:chemistry*; D003598:Cytoskeletal Proteins / Q000032:analysis; D003638:Deafness / Q000209:etiology / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006198:Hair Cells, Auditory / Q000737:chemistry; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008465:Mechanoreceptors / Q000737:chemistry*; D051379:Mice; D008815:Mice, Inbred Strains; D008840:Microfilament Proteins / Q000032:analysis* / Q000378:metabolism; D008871:Microvilli / Q000737:chemistry; D011108:Polymers; D011392:Proline / Q000378:metabolism; D020033:Protein Isoforms / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014162:Transfection; D010738:Type C Phospholipases / Q000378:metabolism; D015837:Vestibular Diseases / Q000209:etiology / Q000378:metabolism
chemical_list: D000199:Actins; D003598:Cytoskeletal Proteins; C472022:Espn protein, rat; D008840:Microfilament Proteins; D011108:Polymers; D020033:Protein Isoforms; C104108:espin protein, mouse; D011392:Proline; D010738:Type C Phospholipases; D002118:Calcium