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 Ca2+-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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 5445-5456 |
| Number of pages | 12 |
| Journal | Journal of Neuroscience |
| Volume | 24 |
| Issue number | 23 |
| DOIs | |
| State | Published - Jun 9 2004 |
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Keywords
- Merkel cell
- Müller cell
- PIP2
- SH3 domain
- Taste cell
- Vomeronasal organ
ASJC Scopus subject areas
- Neuroscience(all)
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}
Espins are multifunctional actin cytoskeletal regulatory proteins in the microvilli of chemosensory and mechanosensory cells. / Sekerková, Gabriella; Zheng, Lili; Loomis, Patricia A.; Changyaleket, Benjarat; Whitlon, Donna S.; Mugnaini, Enrico; Bartles, James R.
In: Journal of Neuroscience, Vol. 24, No. 23, 09.06.2004, p. 5445-5456.Research output: Contribution to journal › Article
TY - JOUR
T1 - Espins are multifunctional actin cytoskeletal regulatory proteins in the microvilli of chemosensory and mechanosensory cells
AU - Sekerková, Gabriella
AU - Zheng, Lili
AU - Loomis, Patricia A.
AU - Changyaleket, Benjarat
AU - Whitlon, Donna S.
AU - Mugnaini, Enrico
AU - Bartles, James R.
PY - 2004/6/9
Y1 - 2004/6/9
N2 - 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 Ca2+-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.
AB - 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 Ca2+-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.
KW - Merkel cell
KW - Müller cell
KW - PIP2
KW - SH3 domain
KW - Taste cell
KW - Vomeronasal organ
UR - http://www.scopus.com/inward/record.url?scp=2942585053&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=2942585053&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.1279-04.2004
DO - 10.1523/JNEUROSCI.1279-04.2004
M3 - Article
C2 - 15190118
AN - SCOPUS:2942585053
VL - 24
SP - 5445
EP - 5456
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 23
ER -