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J. Biol. Chem., Vol. 275, Issue 50, 39369-39378, December 15, 2000
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From the The trypanosome cytoskeleton consists almost
entirely of microtubule-based structures. Although
T Lymphocyte-triggering Factor of African Trypanosomes Is
Associated with the Flagellar Fraction of the Cytoskeleton and
Represents a New Family of Proteins That Are Present in Several
Divergent Eukaryotes*
§,
,¶
Department of Biochemistry and
¶ Interdepartmental Genetics Ph.D. Program, University of Iowa,
Iowa City, Iowa 52242
- and 
-tubulin
from Trypanosoma brucei have been well characterized, much
less is known about other cytoskeleton-associated proteins in
trypanosomes. Using biochemical fractionation, we demonstrate here that
T lymphocyte-triggering factor (TLTF) from T. brucei is a
component of the detergent-resistant and Ca2+-resistant
fraction of the parasite cytoskeleton. This fraction contains the
flagellar apparatus and a subset of cytoskeletal protein complexes that
together function in cell motility, cytokinesis, and organelle
inheritance. We also show that TLTF-related genes are present in
several highly divergent eukaryotic organisms. Although the function of
the corresponding proteins is not known, the mammalian TLTF-like gene
(GAS11; growth
arrest-specific gene 11) is
up-regulated in growth-arrested cells and is a candidate tumor
suppressor (Whitmore, S. A., Settasatian, C., Crawford, J.,
Lower, K. M., McCallum, B., Seshadri, R., Cornelisse, C. J., Moerland, E. W., Cleton-Jansen, A. M., Tipping, A. J.,
Mathew, C. G., Savnio, M., Savoia, A., Verlander, P., Auerbach,
A. D., Van Berkel, C., Pronk, J. C., Doggett, N. A., and
Callen, D. F. (1998) Genomics 52, 325-331),
suggestive of a role in coordinating cytoskeleton activities.
Consistent with this possibility, we show that the human GAS11
protein contains a 144-amino acid domain that co-localizes with
microtubules when fused to the green fluorescent protein and expressed
in mammalian cells. These findings suggest that TLTF represents a newly
defined protein family, whose members contribute to cytoskeleton
function in species as diverse as protozoa and mammals.
*
This work was supported in part by National Institutes of
Health (NIH) Research Grant AI40591 (to J. E. D.) and an Individual National Research Service Award Grant AI07511 (to K. L. H.). This work was also supported by the University of Iowa Diabetes and Endocrinology Research Center (NIH Grant DK25295).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Supported by NIH Genetics Training Grant GM08629.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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