Receptor-mediated endocytosis in the procyclic form of Trypanosoma brucei

被引:40
作者
Liu, JY [1 ]
Qiao, XG [1 ]
Du, DY [1 ]
Lee, MGS [1 ]
机构
[1] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA
关键词
D O I
10.1074/jbc.275.16.12032
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In Trypanosomatids, endocytosis and exocytosis occur exclusively at the flagellar pocket, a deep invagination of the plasma membrane where the flagellum extends from the cell. Both bloodstream and procyclic trypanosomes are capable of internalizing macromolecules, However, structures resembling coated vesicles were only identified in bloodstream form and not in procyclic form trypanosomes. Due to the apparent absence of coated vesicles in procyclics, the significance of receptor-mediated endocytosis in procyclic trypanosomes has been considered of minimal importance. We show that the flagellar pocket associated cysteine-rich acidic transmembrane protein (CRAM) may function as an high density lipoprotein receptor in the procyclic form trypanosome. Using anti-CRAM IgG we have characterized the process of CRAM-mediated endocytosis in procyclic form trypanosomes, The wild type procyclic trypanosome binds and internalizes anti-CRAM IgG but not the non-immune IgG in a saturable and time-dependent manner; the binding and uptake of I-125-labeled anti-CRAM IgG are inhibited by excess unlabeled anti-CRAM IgG. Uptake and degradation of anti-CRAM IgG do not occur at 4 degrees C, At 28 degrees C, the internalized anti-CRAM IgG were efficiently degraded through a process that is inhibited by incubation at 4 degrees C and sensitive to the presence of chloroquine. The uptake and degradation of anti-CRAM IgG does not occur in the CRAM null mutant cell line, These results suggested that the uptake of anti-CRAM IgG in the wild type procyclics occurs via receptor-mediated endocytosis of the CRAM protein. Deletion of the cytoplasmic extension of CRAM drastically reduced the degradation but not the binding of anti-CRAM IgG, This result indicated that potential internalization signals may be present in the cytoplasmic extension of CRAM. This is the first time that the importance of receptor-mediated endocytosis in procyclic form trypanosomes has been demonstrated.
引用
收藏
页码:12032 / 12040
页数:9
相关论文
共 45 条
[1]  
BALBER AE, 1990, CRIT REV IMMUNOL, V10, P177
[2]  
BEISIEGEL U, 1981, J BIOL CHEM, V256, P1923
[3]   METABOLISM OF VERY LOW-DENSITY LIPOPROTEIN PROTEINS .1. PRELIMINARY IN-VITRO AND IN-VIVO OBSERVATIONS [J].
BILHEIMER, DW ;
LEVY, RI ;
EISENBERG, S .
BIOCHIMICA ET BIOPHYSICA ACTA, 1972, 260 (02) :212-+
[4]   Surface receptors and transporters of Trypanosoma brucei [J].
Borst, P ;
Fairlamb, AH .
ANNUAL REVIEW OF MICROBIOLOGY, 1998, 52 :745-778
[5]   MOLECULAR-GENETICS OF ANTIGENIC VARIATION [J].
BORST, P .
IMMUNOPARASITOLOGY TODAY-A COMBINED ISSUE OF IMMUNOLOGY TODAY AND PARASITOLOGY TODAY, 1991, (03) :A29-A33
[6]  
BRUN R, 1979, ACTA TROP, V36, P289
[7]   RECEPTORS FOR THE HOST LOW-DENSITY LIPOPROTEINS ON THE HEMOFLAGELLATE TRYPANOSOMA-BRUCEI - PURIFICATION AND INVOLVEMENT IN THE GROWTH OF THE PARASITE [J].
COPPENS, I ;
BAUDHUIN, P ;
OPPERDOES, FR ;
COURTOY, PJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (18) :6753-6757
[8]   RECEPTOR-MEDIATED ENDOCYTOSIS IN THE BLOOD-STREAM FORM OF TRYPANOSOMA-BRUCEI [J].
COPPENS, I ;
OPPERDOES, FR ;
COURTOY, PJ ;
BAUDHUIN, P .
JOURNAL OF PROTOZOOLOGY, 1987, 34 (04) :465-473
[9]   CELLULAR AND GENETIC-ASPECTS OF ANTIGENIC VARIATION IN TRYPANOSOMES [J].
CROSS, GAM .
ANNUAL REVIEW OF IMMUNOLOGY, 1990, 8 :83-110
[10]  
DAVIS CG, 1987, J BIOL CHEM, V262, P4075