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.

doi:10.1523/jneurosci.1279-04.2004

Cited by 81 publications

(181 citation statements)

References 48 publications

Supporting

Mentioning

170

Contrasting

Order By: Relevance

“…1A). Encoded by a single gene, espins are produced in multiple isoforms that differ markedly in size and in their complement of ligandbinding sites [4,6] (fig. 1A).…”

Section: Introduction To Espin Structure and Activitiesmentioning

confidence: 99%

“…1A). Different transcriptional start sites give rise to four major espin isoform size classes, which range from ~110 kDa to ~25 kDa, and are designated 1-4, in order of decreasing size; splice variants are further specified alphabetically [4] (fig. 1A).…”

Section: Introduction To Espin Structure and Activitiesmentioning

confidence: 99%

“…1A). Although present in multiple actin-rich structures, espins are especially prevalent in the PABs of hair cell stereocilia and the microvilli of other sensory cells, where they appear to be distributed uniformly along the PAB at the core [4,5,7].…”

Section: Introduction To Espin Structure and Activitiesmentioning

confidence: 99%

“…All espin isoforms also contain a Wiskott-Aldrich Syndrome protein homology 2 (WH2) domain ( fig. 1A) that binds actin monomer and is required for espin-mediated actin bundle formation [4,13,14]. The major differences between espin isoforms is in their N-terminal peptides, which differ primarily because of differential transcription start-site selection [4] (fig.…”

Section: Introduction To Espin Structure and Activitiesmentioning

confidence: 99%

“…1A). Depending on isoform, the espin N terminus can include 8 ankyrin-like repeats, an additional binding site for F-actin, a binding site for phosphatidylinositol 4,5-bisphosphate (PIP2) and one or more proline-rich peptides, which can bind the profilins or certain SH3 domains [4,15] (fig. 1A).…”

Section: Introduction To Espin Structure and Activitiesmentioning

confidence: 99%

See 4 more Smart Citations

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

Sekerková

Zheng

Loomis

et al. 2006

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

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].

show abstract

“…1A). Encoded by a single gene, espins are produced in multiple isoforms that differ markedly in size and in their complement of ligandbinding sites [4,6] (fig. 1A).…”

Section: Introduction To Espin Structure and Activitiesmentioning

confidence: 99%

Section: Introduction To Espin Structure and Activitiesmentioning

confidence: 99%

Section: Introduction To Espin Structure and Activitiesmentioning

confidence: 99%

Section: Introduction To Espin Structure and Activitiesmentioning

confidence: 99%

Section: Introduction To Espin Structure and Activitiesmentioning

confidence: 99%

See 3 more Smart Citations

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

Sekerková

Zheng

Loomis

et al. 2006

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

show abstract

A novel mutation in the Espin gene causes autosomal recessive nonsyndromic hearing loss but no apparent vestibular dysfunction in a Moroccan family

Boulouiz

Soualhine

et al. 2008

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Balanced levels of Espin are critical for stereociliary growth and length maintenance

Rzadzinska

Schneider

Noben-Trauth

et al. 2005

Cell Motil. Cytoskeleton

View full text Add to dashboard Cite

Hearing and balance depend on microvilli-like actin-based projections of sensory hair cells called stereocilia. Their sensitivity to mechanical displacements on the nanometer scale requires a highly organized hair bundle in which the physical dimension of each stereocilium is tightly controlled. The length and diameter of each stereocilium are established during hair bundle maturation and maintained by life-long continuing dynamic regulation. Here, we studied the role of the actin-bundling protein Espin in stereociliary growth by examining the hair cell stereocilia of Espin-deficient jerker mice (Espn(je)), and the effects of transiently overexpressing Espin in the neuroepithelial cells of the organ of Corti cultures. Using fluorescence scanning confocal and electron microscopy, we found that a lack of Espin results in inhibition of stereociliary growth followed by progressive degeneration of the hair bundle. In contrast, overexpression of Espin induced lengthening of stereocilia and microvilli that mirrored the elongation of the actin filament bundle at their core. Interestingly, Espin deficiency also appeared to influence the localization of Myosin XVa, an unconventional myosin that is normally present at the stereocilia tip at levels proportional to stereocilia length. These results indicate that Espin is important for the growth and maintenance of the actin-based protrusions of inner ear neuroepithelial cells.

show abstract

Espins Are Multifunctional Actin Cytoskeletal Regulatory Proteins in the Microvilli of Chemosensory and Mechanosensory Cells

Cited by 81 publications

References 48 publications

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

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

A novel mutation in the Espin gene causes autosomal recessive nonsyndromic hearing loss but no apparent vestibular dysfunction in a Moroccan family

Balanced levels of Espin are critical for stereociliary growth and length maintenance

Contact Info

Product

Resources

About