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PMID: 14766983 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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 ·2004-02-17 ·Pages 1868-73

Provance DW, Gourley CR, Silan CM, Cameron LC, Shokat KM, Goldenring JR, Shah K, Gillespie PG, Mercer JA

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 N(6)-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.

MeSH Terms
Actins/metabolism Adenosine Diphosphate/metabolism Adenosine Triphosphate/metabolism Amino Acid Sequence Animals Cell Membrane/metabolism Centrioles/metabolism HeLa Cells Humans Models, Biological Molecular Sequence Data Mutation Myosin Type V/antagonists & inhibitors,genetics,metabolism Protein Engineering Protein Transport Rats Receptors, Transferrin/metabolism Transferrin/metabolism
Chemicals
Actins Receptors, Transferrin Transferrin Adenosine Diphosphate Adenosine Triphosphate Myosin Type V
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Provance D William
McLaughlin Research Institute, Great Falls, MT 59405, USA.
Gourley Christopher R
Silan Colleen M
Cameron L C
Shokat Kevan M
Goldenring James R
Shah Kavita
Gillespie Peter G
Mercer John A
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0305895101
Published
2004-02-17
Epub
2004-00-06
Pages
1868-73
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC357019
Subset
IM
Grants
NIDDK NIH HHS · R01 DK048370 · United States
NIBIB NIH HHS · EB001987 · United States
NIDDK NIH HHS · DK38063 · United States
NCRR NIH HHS · RR015583 · United States
NIDDK NIH HHS · DK48370 · United States
NCRR NIH HHS · P20 RR015583 · United States
NIDCD NIH HHS · R01 DC003279 · United States
NIBIB NIH HHS · R01 EB001987 · United States
NIDCD NIH HHS · DC03279 · United States
External Links
PubMed source DOI: 10.1073/pnas.0305895101 PMC Full Text View journal details
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