|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
Research Article |
Department of Cellular Biology, University of Georgia, Athens, Georgia 30602, USA
* Author for correspondence (e-mail: fechheim{at}cb.uga.edu )
Accepted 26 February 2002
We report the serendipitous development of the first cultured cell models
of Hirano bodies. Myc-epitope-tagged forms of the 34 kDa actin bundling
protein (amino acids 1-295) and the CT fragment (amino acids 124-295) of the
34 kDa protein that exhibits activated actin binding and calcium-insensitive
actin filament crosslinking activity were expressed in Dictyostelium
and mammalian cells to assess the behavior of these modified forms in vivo.
Dictyostelium cells expressing the CT-myc fragment: (1) form
ellipsoidal regions that contain ordered assemblies of F-actin, CT-myc, myosin
II, cofilin and
-actinin; (2) grow and develop more slowly than
wildtype, but produce normal morphogenetic structures; (3) perform pinocytosis
and phagocytosis normally; and (4) produce a level of total actin equivalent
to wildtype, but a higher level of F-actin. The paracrystalline inclusions
bear a striking resemblance to Hirano bodies, which are associated with a
number of pathological conditions. Furthermore, expression of the CT fragment
in murine L cells results in F-actin rearrangements characterized by loss of
stress fibers, accumulation of numerous punctate foci, and large perinuclear
aggregates, the Hirano bodies. Thus, failure to regulate the activity and/or
affinity of an actin crosslinking protein can provide a signal for formation
of Hirano bodies. More generally, formation of Hirano bodies is a cellular
response to or a consequence of aberrant function of the actin cytoskeleton.
The results reveal that formation of Hirano bodies is not necessarily related
to cell death. These cultured cell models should facilitate studies of the
biochemistry, genetics and physiological effects of Hirano bodies.
Key words: Cytoskeleton, Actin-binding protein, Dictyostelium, Hirano body, Neurodegeneration
![]()
CiteULike
Complore
Connotea
Del.icio.us
Digg
Reddit
Technorati
Twitter What's this?
This article has been cited by other articles:
![]() |
J. F. Reyes, K. Stone, J. Ramos, and A. Maselli Formation of Hirano Bodies after Inducible Expression of a Modified Form of an Actin-Cross-Linking Protein Eukaryot. Cell, June 1, 2009; 8(6): 852 - 857. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Lazaro-Dieguez, C. Aguado, E. Mato, Y. Sanchez-Ruiz, I. Esteban, J. Alberch, E. Knecht, and G. Egea Dynamics of an F-actin aggresome generated by the actin-stabilizing toxin jasplakinolide J. Cell Sci., May 1, 2008; 121(9): 1415 - 1425. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. D. Johnson, L.-R. Yu, T. P. Conrads, Y. Kinoshita, T. Uo, J. D. Matthews, S.-W. Lee, R. D. Smith, T. D. Veenstra, and R. S. Morrison Proteome Analysis of DNA Damage-induced Neuronal Death Using High Throughput Mass Spectrometry J. Biol. Chem., June 18, 2004; 279(25): 26685 - 26697. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Iwai, A. Ishiji, I. Mabuchi, and K. Sutoh A Novel Actin-bundling Kinesin-related Protein from Dictyostelium discoideum J. Biol. Chem., February 6, 2004; 279(6): 4696 - 4704. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Maselli, R. Furukawa, S. A. M. Thomson, R. C. Davis, and M. Fechheimer Formation of Hirano Bodies Induced by Expression of an Actin Cross-Linking Protein with a Gain-of-Function Mutation Eukaryot. Cell, August 1, 2003; 2(4): 778 - 787. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Furukawa, A. Maselli, S. A. M. Thomson, R. W. L. Lim, J. V. Stokes, and M. Fechheimer Calcium regulation of actin crosslinking is important for function of the actin cytoskeleton in Dictyostelium J. Cell Sci., January 1, 2003; 116(1): 187 - 196. [Abstract] [Full Text] [PDF] |
||||