title: Calcium triggers exocytosis from two types of organelles in a single astrocyte.
abstract: Astrocytes release a variety of signaling molecules including glutamate, D-serine, and ATP in a regulated manner. Although the functions of these molecules, from regulating synaptic transmission to controlling specific behavior, are well documented, the identity of their cellular compartment(s) is still unclear. Here we set out to study vesicular exocytosis and glutamate release in mouse hippocampal astrocytes. We found that small vesicles and lysosomes coexisted in the same freshly isolated or cultured astrocytes. Both small vesicles and lysosome fused with the plasma membrane in the same astrocytes in a Ca(2+)-regulated manner, although small vesicles were exocytosed more efficiently than lysosomes. Blockade of the vesicle glutamate transporter or cleavage of synaptobrevin 2 and cellubrevin (both are vesicle-associated membrane proteins) with a clostridial toxin greatly inhibited glutamate release from astrocytes, while lysosome exocytosis remained intact. Thus, both small vesicles and lysosomes contribute to Ca(2+)-dependent vesicular exocytosis, and small vesicles support glutamate release from astrocytes.
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Sun
authors.forename: Yingfei
authors.initials: Y
authors.lastname: Xiong
authors.forename: Shujiang
authors.initials: S
authors.lastname: Shang
authors.forename: Ning
authors.initials: N
authors.lastname: Guo
authors.forename: Sasa
authors.initials: S
authors.lastname: Teng
authors.forename: Yeshi
authors.initials: Y
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Changhe
authors.initials: C
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Lianghong
authors.initials: L
authors.lastname: Zheng
authors.forename: Claire Xi
authors.initials: CX
authors.lastname: Zhang
authors.forename: Weiping
authors.initials: W
authors.lastname: Han
authors.forename: Zhuan
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000648:ultrastructure*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005089:Exocytosis / Q000187:drug effects* / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein; D018698:Glutamic Acid / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics; D009498:Neurotoxins / Q000494:pharmacology; D017470:Receptors, Glutamate / Q000235:genetics; D013744:Tetanus Toxin / Q000494:pharmacology; D014162:Transfection / Q000379:methods; D022161:Transport Vesicles / Q000187:drug effects / Q000378:metabolism*; D050988:Vesicle-Associated Membrane Protein 2 / Q000235:genetics / Q000378:metabolism; D051040:Vesicle-Associated Membrane Protein 3 / Q000378:metabolism; D050598:Vesicular Glutamate Transport Protein 1 / Q000235:genetics
chemical_list: D005904:Glial Fibrillary Acidic Protein; D052118:Lysosomal-Associated Membrane Protein 1; D009498:Neurotoxins; D017470:Receptors, Glutamate; D013744:Tetanus Toxin; C494807:VAMP2 protein, human; D050988:Vesicle-Associated Membrane Protein 2; D051040:Vesicle-Associated Membrane Protein 3; D050598:Vesicular Glutamate Transport Protein 1; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D018698:Glutamic Acid; D002118:Calcium