Identification of soluble N-ethylmaleimide-sensitive factor attachment protein receptor exocytotic machinery in human plasma cells:: SNAP-23 is essential for antibody secretion

被引:33
作者
Reales, E [1 ]
Mora-López, F [1 ]
Rivas, V [1 ]
García-Poley, A [1 ]
Brieva, JA [1 ]
Campos-Caro, A [1 ]
机构
[1] Hosp Univ Puerta Mar, Unidad Invest, Cadiz 11009, Spain
关键词
D O I
10.4049/jimmunol.175.10.6686
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Plasma cells (PC) are B-lymphocytes terminally differentiated in a postmitotic state, with the unique purpose of manufacturing and exporting Igs. Despite the importance of this process in the survival of vertebrates, no studies have been made to understand the molecular events that regulate Ig exocytosis by PC. The present study explores the possible presence of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) system in human PC, and examines its functional role in Ig secretion. Syntaxin-2, Syntaxin-3, Syntaxin-4, vesicle-associated membrane protein (VAMP)-2, VAMP-3, and synaptosome-associated protein (SNAP)-23 could be readily detected in normal human PC obtained from intestinal lamina propria and blood, as well as in human PC lines. Because SNAP-23 plays a central role in SNAREs complex formation, it was chosen to examine possible functional implications of the SNARE system in PC Ig secretion. When recombinant SNAP-23 fusion protein was introduced into the cells, a complete abolishment of Ig production was observed in the culture supernatants of PC lines, as well as in those of normal PC. These results provide insights, for the first time, into the molecular machinery of constitutive vesicular trafficking in human PC Ig secretion and present evidence indicating that at least SNAP-23 is essential for Ab production.
引用
收藏
页码:6686 / 6693
页数:8
相关论文
共 58 条
[1]   DIFFERENTIAL EXPRESSION OF SNAP-25 PROTEIN ISOFORMS DURING DIVERGENT VESICLE FUSION EVENTS OF NEURAL DEVELOPMENT [J].
BARK, IC ;
HAHN, KM ;
RYABININ, AE ;
WILSON, MC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (05) :1510-1514
[2]   THE MOLECULAR MACHINERY FOR SECRETION IS CONSERVED FROM YEAST TO NEURONS [J].
BENNETT, MK ;
SCHELLER, RH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (07) :2559-2563
[3]   SNARES AND THE SPECIFICITY OF TRANSPORT VESICLE TARGETING [J].
BENNETT, MK .
CURRENT OPINION IN CELL BIOLOGY, 1995, 7 (04) :581-586
[4]   The mechanisms of vesicle budding and fusion [J].
Bonifacino, JS ;
Glick, BS .
CELL, 2004, 116 (02) :153-166
[5]   HUMAN TONSIL, BLOOD AND BONE-MARROW IN-VIVO INDUCED B-CELLS CAPABLE OF SPONTANEOUS AND HIGH-RATE IMMUNOGLOBULIN SECRETION IN-VITRO - DIFFERENCES IN THE REQUIREMENTS FOR FACTORS AND FOR ADHERENT AND BONE-MARROW STROMAL CELLS, AS WELL AS DISTINCTIVE ADHESION MOLECULE EXPRESSION [J].
BRIEVA, JA ;
ROLDAN, E ;
RODRIGUEZ, C ;
NAVAS, G .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1994, 24 (02) :362-366
[6]  
BRUMELL JH, 1995, J IMMUNOL, V155, P5750
[7]  
BURGESS TL, 1987, ANNU REV CELL BIOL, V3, P243, DOI 10.1146/annurev.cb.03.110187.001331
[8]   Phosphorylation of SNAP-23 by the novel kinase SNAK regulates t-SNARE complex assembly [J].
Cabaniols, JP ;
Ravichandran, V ;
Roche, PA .
MOLECULAR BIOLOGY OF THE CELL, 1999, 10 (12) :4033-4041
[9]   Regulatory mechanisms that determine the development and function of plasma cells [J].
Calame, KL ;
Lin, KI ;
Tunyaplin, C .
ANNUAL REVIEW OF IMMUNOLOGY, 2003, 21 :205-230
[10]  
CHOMCZYNSKI P, 1987, ANAL BIOCHEM, V162, P156, DOI 10.1016/0003-2697(87)90021-2