|
|
 Previous Article | Table of Contents | Next Article 
Blood, 1 October 2002, Vol. 100, No. 7, pp. 2629-2636
RED CELLS
A splicing alteration of 4.1R pre-mRNA generates 2 protein
isoforms with distinct assembly to spindle poles in mitotic
cells
François Delhommeau,
Corinne Vasseur-Godbillon,
Philippe Leclerc,
Pierre-Olivier Schischmanoff,
Laure Croisille,
Patricia Rince,
Madeleine Morinière,
Edward J. Benz Jr,
Gil Tchernia,
Gabriel Tamagnini,
Leticia Ribeiro,
Jean Delaunay, and
Faouzi Baklouti
From Institut National de la Santé et de
la Recherche Médicale, U 473 and U 488; the Service de Biochimie
I, Hôpital de Bicêtre, Assistance Publique-Hôpitaux
de Paris; and the Service d'Hématologie d'Immunologie et de
Cytogénétique, Assistance Publique, Le
Kremlin-Bicêtre, France; Institut National de la Sante et de la
Recherche Medicale U 362, Institut Gustave-Roussy, Villejuif, France;
Centre National de la Recherche Scientifique UMR 5534, Centre de
Génétique Moléculaire et Cellulaire, Université
Lyon I, Villeurbanne, France; Dana-Farber/Harvard Cancer Center, and
the Department of Medicine, Brigham and Women's Hospital; the
Department of Pediatrics, Children's Hospital of Boston, and Harvard
Medical School, Boston, MA; and the Serviço de Hematologia,
Centro Hospitalar de Coimbra, Portugal.
The C-terminal region of erythroid cytoskeletal protein 4.1R,
encoded by exons 20 and 21, contains a binding site for nuclear mitotic
apparatus protein (NuMA), a protein needed for the formation and stabilization of the mitotic spindle. We have previously described a splicing mutation of 4.1R that yields 2 isoforms: One, CO.1, lacks
most of exon 20-encoded peptide and carries a missense C-terminal sequence. The other, CO.2, lacks exon 20-encoded C-terminal
sequence, but retains the normal exon 21-encoded C-terminal
sequence. Knowing that both shortened proteins are expressed in red
cells and assemble to the membrane skeleton, we asked whether they
would ensure 4.1R mitotic function in dividing cells. We show here that
CO.2, but not CO.1, assembles to spindle poles, and colocalizes with
NuMA in erythroid and lymphoid mutated cells, but none of these
isoforms interact with NuMA in vitro. In microtubule-destabilizing
conditions, again only CO.2 localizes to the centrosomes. These data
suggest that the stability of 4.1R association with centrosomes
requires an intact C-terminal end, either for a proper conformation of the protein, for a direct binding to an unknown centrosome-cytoskeletal network, or for both. We also found that 4.1G, a ubiquitous
homolog of 4.1R, is present in mutated as well as control cells and
that its C-terminal region binds efficiently to NuMA,
suggesting that in fact mitotic spindles host a mixture of the two 4.1 family members. These findings led to the postulate that the
coexpression at the spindle poles of 2 related proteins, 4.1R and 4.1G,
might reflect a functional redundancy in mitotic cells.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
S. W. Krauss, J. R. Spence, S. Bahmanyar, A. I. M. Barth, M. M. Go, D. Czerwinski, and A. J. Meyer
Downregulation of Protein 4.1R, a Mature Centriole Protein, Disrupts Centrosomes, Alters Cell Cycle Progression, and Perturbs Mitotic Spindles and Anaphase
Mol. Cell. Biol.,
April 1, 2008;
28(7):
2283 - 2294.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-C. Huang, E. S. Liu, S.-H. Chan, I. D. Munagala, H. T. Cho, R. Jagadeeswaran, and E. J. Benz Jr
Mitotic Regulation of Protein 4.1R Involves Phosphorylation by cdc2 Kinase
Mol. Biol. Cell,
January 1, 2005;
16(1):
117 - 127.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. W. Krauss, G. Lee, J. A. Chasis, N. Mohandas, and R. Heald
Two Protein 4.1 Domains Essential for Mitotic Spindle and Aster Microtubule Dynamics and Organization in Vitro
J. Biol. Chem.,
June 25, 2004;
279(26):
27591 - 27598.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
