Vesicular Calcium Regulates Coat Retention, Fusogenicity, and Size of Pre-Golgi Intermediates

被引:43
|
作者
Bentley, Marvin [1 ,2 ]
Nycz, Deborah C. [1 ,2 ]
Joglekar, Ashwini [3 ]
Fertschai, Ismene [4 ]
Malli, Roland [4 ]
Graier, Wolfgang F. [4 ]
Hay, Jesse C. [1 ,2 ]
机构
[1] Univ Montana, Div Biol Sci, Missoula, MT 59812 USA
[2] Univ Montana, Ctr Struct & Funct Neurosci, Missoula, MT 59812 USA
[3] Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA
[4] Med Univ Graz, Ctr Mol Med, A-8010 Graz, Austria
基金
美国国家卫生研究院;
关键词
RETICULUM EXIT SITES; ENDOPLASMIC-RETICULUM; COPII VESICLES; FLUORESCENT INDICATORS; PROTEIN ALG-2; CA2+; ER; TRANSPORT; MEMBRANE; LOCALIZATION;
D O I
10.1091/mbc.E09-10-0914
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The significance and extent of Ca2+ regulation of the biosynthetic secretory pathway have been difficult to establish, and our knowledge of regulatory relationships integrating Ca2+ with vesicle coats and function is rudimentary. Here, we investigated potential roles and mechanisms of luminal Ca2+ in the early secretory pathway. Specific depletion of luminal Ca2+ in living normal rat kidney cells using cyclopiazonic acid (CPA) resulted in the extreme expansion of vesicular tubular cluster (VTC) elements. Consistent with this, a suppressive role for vesicle-associated Ca2+ in COPII vesicle homotypic fusion was demonstrated in vitro using Ca2+ chelators. The EF-hand-containing protein apoptosis-linked gene 2 (ALG-2), previously implicated in the stabilization of sec31 at endoplasmic reticulum exit sites, inhibited COPII vesicle fusion in a Ca2+-requiring manner, suggesting that ALG-2 may be a sensor for the effects of vesicular Ca2+ on homotypic fusion. Immunoisolation established that Ca2+ chelation inhibits and ALG-2 specifically favors residual retention of the COPII outer shell protein sec31 on pre-Golgi fusion intermediates. We conclude that vesicle-associated Ca2+, acting through ALG-2, favors the retention of residual coat molecules that seem to suppress membrane fusion. We propose that in cells, these Ca2+-dependent mechanisms temporally regulate COPII vesicle interactions, VTC biogenesis, cargo sorting, and VTC maturation.
引用
收藏
页码:1033 / 1046
页数:14
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