A novel allele of myosin VIIa reveals a critical function for the C-terminal FERM domain for melanosome transport in retinal pigment epithelial cells

Martin Schwander, Vanda Lopes, Anna Sczaniecka, Daniel Gibbs, Concepcion Lillo, David Delano, Lisa M. Tarantino, Tim Wiltshire, David S. Williams, Ulrich Mueller

Research output: Contribution to journalArticle

Abstract

Mutations in the head and tail domains of the motor protein myosin VIIA (MYO7A) cause deaf-blindness (Usher syndrome type 1B, USH1B) and nonsyndromic deafness (DFNB2, DFNA11). The head domain binds to F-actin and serves as the MYO7A motor domain, but little is known about the function of the tail domain. In a genetic screen, we have identified polka mice, which carry a mutation (c.5742 + 5G > A) that affects splicing of the MYO7A transcript and truncates the MYO7A tail domain at the C-terminal FERM domain. In the inner ear, expression of the truncated MYO7A protein is severely reduced, leading to defects in hair cell development. In retinal pigment epithelial (RPE) cells, the truncated MYO7A protein is expressed at comparative levels to wild-type protein but fails to associate with and transport melanosomes. We conclude that the C-terminal FERM domain of MYO7A is critical for melanosome transport in RPE cells. Our findings also suggest that MYO7A mutations can lead to tissue-specific effects on protein levels, which may explain why some mutations in MYO7A lead to deafness without retinal impairment.

Original languageEnglish (US)
Pages (from-to)15810-15818
Number of pages9
JournalJournal of Neuroscience
Volume29
Issue number50
DOIs
StatePublished - Dec 16 2009
Externally publishedYes

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Melanosomes
Retinal Pigments
Epithelial Cells
Alleles
Mutation
Tail
Head
Deafness
Inner Ear
Blindness
Myosins
Actins
Proteins
myosin VIIa

ASJC Scopus subject areas

  • Neuroscience(all)

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A novel allele of myosin VIIa reveals a critical function for the C-terminal FERM domain for melanosome transport in retinal pigment epithelial cells. / Schwander, Martin; Lopes, Vanda; Sczaniecka, Anna; Gibbs, Daniel; Lillo, Concepcion; Delano, David; Tarantino, Lisa M.; Wiltshire, Tim; Williams, David S.; Mueller, Ulrich.

In: Journal of Neuroscience, Vol. 29, No. 50, 16.12.2009, p. 15810-15818.

Research output: Contribution to journalArticle

Schwander, M, Lopes, V, Sczaniecka, A, Gibbs, D, Lillo, C, Delano, D, Tarantino, LM, Wiltshire, T, Williams, DS & Mueller, U 2009, 'A novel allele of myosin VIIa reveals a critical function for the C-terminal FERM domain for melanosome transport in retinal pigment epithelial cells', Journal of Neuroscience, vol. 29, no. 50, pp. 15810-15818. https://doi.org/10.1523/JNEUROSCI.4876-09.2009
Schwander, Martin ; Lopes, Vanda ; Sczaniecka, Anna ; Gibbs, Daniel ; Lillo, Concepcion ; Delano, David ; Tarantino, Lisa M. ; Wiltshire, Tim ; Williams, David S. ; Mueller, Ulrich. / A novel allele of myosin VIIa reveals a critical function for the C-terminal FERM domain for melanosome transport in retinal pigment epithelial cells. In: Journal of Neuroscience. 2009 ; Vol. 29, No. 50. pp. 15810-15818.
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