Skip to main content

Rod mutations associated with MYH9-related disorders disrupt nonmuscle myosin-IIA assembly.

Publication ,  Journal Article
Franke, JD; Dong, F; Rickoll, WL; Kelley, MJ; Kiehart, DP
Published in: Blood
January 1, 2005

MYH9-related disorders are autosomal dominant syndromes, variably affecting platelet formation, hearing, and kidney function, and result from mutations in the human nonmuscle myosin-IIA heavy chain gene. To understand the mechanisms by which mutations in the rod region disrupt nonmuscle myosin-IIA function, we examined the in vitro behavior of 4 common mutant forms of the rod (R1165C, D1424N, E1841K, and R1933Stop) compared with wild type. We used negative-stain electron microscopy to analyze paracrystal morphology, a model system for the assembly of individual myosin-II molecules into bipolar filaments. Wild-type tail fragments formed ordered paracrystal arrays, whereas mutants formed aberrant aggregates. In mixing experiments, the mutants act dominantly to interfere with the proper assembly of wild type. Using circular dichroism, we find that 2 mutants affect the alpha-helical coiled-coil structure of individual molecules, and 2 mutants disrupt the lateral associations among individual molecules necessary to form higher-order assemblies, helping explain the dominant effects of these mutants. These results demonstrate that the most common mutations in MYH9, lesions in the rod, cause defects in nonmuscle myosin-IIA assembly. Further, the application of these methods to biochemically characterize rod mutations could be extended to other myosins responsible for disease.

Duke Scholars

Published In

Blood

DOI

ISSN

0006-4971

Publication Date

January 1, 2005

Volume

105

Issue

1

Start / End Page

161 / 169

Location

United States

Related Subject Headings

  • Temperature
  • Salts
  • Retinal Rod Photoreceptor Cells
  • Nonmuscle Myosin Type IIA
  • Mutation
  • Microscopy, Electron
  • Immunology
  • DNA Glycosylases
  • Circular Dichroism
  • 3213 Paediatrics
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Franke, J. D., Dong, F., Rickoll, W. L., Kelley, M. J., & Kiehart, D. P. (2005). Rod mutations associated with MYH9-related disorders disrupt nonmuscle myosin-IIA assembly. Blood, 105(1), 161–169. https://doi.org/10.1182/blood-2004-06-2067
Franke, Josef D., Fan Dong, Wayne L. Rickoll, Michael J. Kelley, and Daniel P. Kiehart. “Rod mutations associated with MYH9-related disorders disrupt nonmuscle myosin-IIA assembly.Blood 105, no. 1 (January 1, 2005): 161–69. https://doi.org/10.1182/blood-2004-06-2067.
Franke JD, Dong F, Rickoll WL, Kelley MJ, Kiehart DP. Rod mutations associated with MYH9-related disorders disrupt nonmuscle myosin-IIA assembly. Blood. 2005 Jan 1;105(1):161–9.
Franke, Josef D., et al. “Rod mutations associated with MYH9-related disorders disrupt nonmuscle myosin-IIA assembly.Blood, vol. 105, no. 1, Jan. 2005, pp. 161–69. Pubmed, doi:10.1182/blood-2004-06-2067.
Franke JD, Dong F, Rickoll WL, Kelley MJ, Kiehart DP. Rod mutations associated with MYH9-related disorders disrupt nonmuscle myosin-IIA assembly. Blood. 2005 Jan 1;105(1):161–169.

Published In

Blood

DOI

ISSN

0006-4971

Publication Date

January 1, 2005

Volume

105

Issue

1

Start / End Page

161 / 169

Location

United States

Related Subject Headings

  • Temperature
  • Salts
  • Retinal Rod Photoreceptor Cells
  • Nonmuscle Myosin Type IIA
  • Mutation
  • Microscopy, Electron
  • Immunology
  • DNA Glycosylases
  • Circular Dichroism
  • 3213 Paediatrics