O-glycosylation is essential for intracellular targeting of synaptotagmins I and II in non-neuronal specialized secretory cells

被引:13
作者
Atiya-Nasagi, Y
Cohen, H
Medalia, O
Fukuda, M
Sagi-Eisenberg, R [1 ]
机构
[1] Tel Aviv Univ, Sackler Sch Med, Dept Cell & Dev Biol, IL-69978 Tel Aviv, Israel
[2] RIKEN, Fukuda Initiat Res Unit, Wako, Saitama 3510198, Japan
关键词
sorting; glycosylation; synaptotagmin; RBL-2H3;
D O I
10.1242/jcs.01710
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
We have examined the trafficking of synaptotagmin (Syt) I and II in the mast cell line rat basophilic leukemia (RBL2H3). We demonstrate that both Syt I and Syt II travel through the plasma membrane and require endocytosis to reach their final intracellular localization. However, N- or C-terminal tagging of Syt II, but not of Syt I, prevents its internalization, trapping the tagged protein at the plasma membrane. Furthermore, a chimeric protein comprising a tagged luminal domain of Syt II fused with the remaining domains of Syt I also localizes to the plasma membrane, whereas a chimera consisting of tagged luminal domain of Syt I fused with Syt II colocalizes with Syt I on secretory granules. We also show that endocytosis of both Syt I and Syt II is strictly dependent on O-glycosylation processing, whereby O-glycosylation mutants of either protein fail to internalize and remain at the plasma membrane. Our results indicate that the luminal domains of Syt I and Syt II govern their internalization capacity from the plasma membrane and identify O-glycosylation as playing a crucial role in Syt trafficking in non-neuronal secretory cells.
引用
收藏
页码:1363 / 1372
页数:10
相关论文
共 42 条
  • [1] O-linked glycans mediate apical sorting of human intestinal sucrase-isomaltase through association with lipid rafts
    Alfalah, M
    Jacob, R
    Preuss, U
    Zimmer, KP
    Naim, H
    Naim, HY
    [J]. CURRENT BIOLOGY, 1999, 9 (11) : 593 - 596
  • [2] Baram D, 1998, J IMMUNOL, V161, P5120
  • [3] Synaptotagmin II negatively regulates Ca2+-triggered exocytosis of lysosomes in mast cells
    Baram, D
    Adachi, R
    Medalia, O
    Tuvim, M
    Dickey, BF
    Mekori, YA
    Sagi-Eisenberg, R
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 189 (10) : 1649 - 1657
  • [4] Geldanamycin-associated inhibition of intracellular trafficking is attributed to a co-purified activity
    Barzilay, E
    Ben-Califa, N
    Supino-Rosin, L
    Kashman, Y
    Hirschberg, K
    Elazar, Z
    Neumann, D
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (08) : 6847 - 6852
  • [5] BONIFACINO JS, 1989, J CELL SCI, V92, P701
  • [6] SYNAPTOTAGMIN - A CALCIUM SENSOR ON THE SYNAPTIC VESICLE SURFACE
    BROSE, N
    PETRENKO, AG
    SUDHOF, TC
    JAHN, R
    [J]. SCIENCE, 1992, 256 (5059) : 1021 - 1025
  • [7] Internalization signals in synaptotagmin VII utilizing two independent pathways are masked by intramolecular inhibitions
    Dasgupta, S
    Kelly, RB
    [J]. JOURNAL OF CELL SCIENCE, 2003, 116 (07) : 1327 - 1337
  • [8] Lysosome-related organelles
    Dell'Angelica, EC
    Mullins, C
    Caplan, S
    Bonifacino, JS
    [J]. FASEB JOURNAL, 2000, 14 (10) : 1265 - 1278
  • [9] THE SYNAPTIC VESICLE PROTEINS SV2, SYNAPTOTAGMIN AND SYNAPTOPHYSIN ARE SORTED TO SEPARATE CELLULAR COMPARTMENTS IN CHO FIBROBLASTS
    FEANY, MB
    YEE, AG
    DELVY, ML
    BUCKLEY, KM
    [J]. JOURNAL OF CELL BIOLOGY, 1993, 123 (03) : 575 - 584
  • [10] Vesicle-associated membrane protein-2/Synaptobrevin binding to Synaptotagmin I promotes O-glycosylation of Synaptotagmin I
    Fukuda, M
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (33) : 30351 - 30358