Chemical-genetic inhibition of a sensitized mutant myosin Vb demonstrates a role in peripheral-pericentriolar membrane traffic

D. William Provance; Christopher R. Gourley; Colleen M. Silan; L. C. Cameron; Kevan M. Shokat; James R. Goldenring; Kavita Shah; Peter G. Gillespie; John A. Mercer

doi:10.1073/pnas.0305895101

Chemical-genetic inhibition of a sensitized mutant myosin Vb demonstrates a role in peripheral-pericentriolar membrane traffic

D. William Provance, Christopher R. Gourley, Colleen M. Silan, L. C. Cameron, Kevan M. Shokat, James R. Goldenring, Kavita Shah, Peter G. Gillespie, John A. Mercer

Otolaryngology

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Abstract

Selective, in situ inhibition of individual unconventional myosins is a powerful approach to determine their specific physiological functions. Here, we report the engineering of a myosin Vb mutant that still hydrolyzes ATP, yet is selectively sensitized to an N⁶-substituted ADP analog that inhibits its activity, causing it to remain tightly bound to actin. Inhibition of the sensitized mutant causes inhibition of accumulation of transferrin in the cytoplasm and increases levels of plasma-membrane transferrin receptor, suggesting that myosin Vb functions in traffic between peripheral and pericentrosomal compartments.

Original language	English (US)
Pages (from-to)	1868-1873
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	101
Issue number	7
DOIs	https://doi.org/10.1073/pnas.0305895101
State	Published - Feb 17 2004

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Provance, D. W., Gourley, C. R., Silan, C. M., Cameron, L. C., Shokat, K. M., Goldenring, J. R., Shah, K., Gillespie, P. G., & Mercer, J. A. (2004). Chemical-genetic inhibition of a sensitized mutant myosin Vb demonstrates a role in peripheral-pericentriolar membrane traffic. Proceedings of the National Academy of Sciences of the United States of America, 101(7), 1868-1873. https://doi.org/10.1073/pnas.0305895101

Chemical-genetic inhibition of a sensitized mutant myosin Vb demonstrates a role in peripheral-pericentriolar membrane traffic. / Provance, D. William; Gourley, Christopher R.; Silan, Colleen M. et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 7, 17.02.2004, p. 1868-1873.

Research output: Contribution to journal › Article › peer-review

Provance, DW, Gourley, CR, Silan, CM, Cameron, LC, Shokat, KM, Goldenring, JR, Shah, K, Gillespie, PG & Mercer, JA 2004, 'Chemical-genetic inhibition of a sensitized mutant myosin Vb demonstrates a role in peripheral-pericentriolar membrane traffic', Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 7, pp. 1868-1873. https://doi.org/10.1073/pnas.0305895101

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AU - Shokat, Kevan M.

AU - Goldenring, James R.

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AU - Mercer, John A.

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Chemical-genetic inhibition of a sensitized mutant myosin Vb demonstrates a role in peripheral-pericentriolar membrane traffic

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