Calcium Triggers Exocytosis from Two Types of Organelles in a Single Astrocyte

Liu, Tao; Sun, Lei; Xiong, Yong; Shang, Shujiang; Guo, Na; Teng, Susanto; Wang, Yeshi; Liu, Bin; Wang, Changhe; Wang, Li; Zheng, Lianghong; Zhang, Claire Xi; Han, Weiping; Zhou, Zhuan

doi:10.1523/jneurosci.6401-10.2011

Cited by 87 publications

(142 citation statements)

References 62 publications

(120 reference statements)

Supporting

Mentioning

130

Contrasting

Order By: Relevance

“…11,12,20,44 We show that astrocyte cell membrane injury causes a greater [Ca 2+ ] c increase, triggering more robust lysosome exocytosis. Receptor stimulation causes a sustained and low rate of exocytosis where lysosomes release a part of their luminal content and none of their membrane proteins (Figures 2 and 6).…”

Section: Discussionmentioning

confidence: 68%

Injured astrocytes are repaired by Synaptotagmin XI-regulated lysosome exocytosis

et al. 2015

View full text Add to dashboard Cite

Astrocytes are known to facilitate repair following brain injury; however, little is known about how injured astrocytes repair themselves. Repair of cell membrane injury requires Ca 2+ -triggered vesicle exocytosis. In astrocytes, lysosomes are the main Ca 2+ -regulated exocytic vesicles. Here we show that astrocyte cell membrane injury results in a large and rapid calcium increase. This triggers robust lysosome exocytosis where the fusing lysosomes release all luminal contents and merge fully with the plasma membrane. In contrast to this, receptor stimulation produces a small sustained calcium increase, which is associated with partial release of the lysosomal luminal content, and the lysosome membrane does not merge into the plasma membrane. In most cells, lysosomes express the synaptotagmin (Syt) isoform Syt VII; however, this isoform is not present on astrocyte lysosomes and exogenous expression of Syt VII on lysosome inhibits their exocytosis. Deletion of one of the most abundant Syt isoform in astrocyte -Syt XI -suppresses astrocyte lysosome exocytosis. This identifies lysosome as Syt XI-regulated exocytic vesicle in astrocytes. Further, inhibition of lysosome exocytosis (by Syt XI depletion or Syt VII expression) prevents repair of injured astrocytes. These results identify the lysosomes and Syt XI as the sub-cellular and molecular regulators, respectively of astrocyte cell membrane repair.

show abstract

Section: Discussionmentioning

confidence: 68%

Injured astrocytes are repaired by Synaptotagmin XI-regulated lysosome exocytosis

et al. 2015

View full text Add to dashboard Cite

show abstract

“…However, quinacrine also binds ATP with a high affinity (23,24) and is commonly used to visualize ATP-containing vesicles, including lysosomes (6,7,25,26). We provide new evi- dence that quinacrine intensity correlates with lysosomal ATP levels rather than lysosomal acidic pH.…”

Section: Discussionmentioning

confidence: 88%

“…Therefore, in these cells, lysosomes may be the major secretory vesicles that release ATP. Previously, others have reported that ATP accumulated in lysosomes of astrocytes (6,26) and microglia (7) and lysosomal ATP release via lysosomal exocytosis is implicated in ischemic insult (6) and cell migration (7). However, the molecular mechanisms underlying ATP accumulation in these cells remain elusive.…”

Section: Discussionmentioning

confidence: 99%

SLC17A9 Protein Functions as a Lysosomal ATP Transporter and Regulates Cell Viability

Cao

Zhao

Zhong

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Lysosomes contain abundant ATP. Results: SLC17A9 transports ATP into lysosomes. SLC17A9-deficient cells exhibit lysosome dysfunction and undergo subsequent cell death. Conclusion: SLC17A9 functions as a lysosomal ATP transporter and maintains cell viability. Significance: This work identifies a molecular mechanism underlying lysosomal ATP accumulation and suggests that ATP functions not only as energy currency but plays a key role in lysosome function.

show abstract

“…Upon stimulation, lysosomes translocate from the perinuclear and cytosolic regions to the plasma membrane along the microtubules (33)(34)(35)(36). After docking, lysosomes fuse directly with the plasma membrane to release the lysosomal content into the extracellular space ( Fig.…”

Section: Lysosomal Lipid Storage Disordersmentioning

confidence: 99%

Lysosomal exocytosis and lipid storage disorders

Samie

2014

Journal of Lipid Research

146

178

View full text Add to dashboard Cite

respective smaller building-block molecules: amino acids, monosaccharides, free fatty acids, or nucleotides ( 1-4 ). Hence, since their discovery by Christian De Duve in 1955, lysosomes have been viewed as the cell's degradation center ( 3,5 ). Lysosomes, several hundreds of them in each mammalian cell, are heterogeneous in size (100-1,000 nm) and morphology, and collectively constitute ‫ف‬ 5% of the cell volume ( 6 ). Lysosomes are filled with more than 50 different types of hydrolases: sulphatases, phosphatases, lipases, proteases, carbohydrases, and glycosidases, which effectively catabolize proteins and complex lipids into their building-block molecules ( 1, 4 ). The functions of most lysosomal hydrolytic enzymes require an acidic lumen, which is established and maintained by the vacuolarATPase (V-ATPase)... proton pumps located on the perimeter limited membrane ( 6 ). To protect the perimeter membrane and its resident membrane proteins from degradation, the inner leafl et of the lysosomal membrane is coated with a polysaccharide layer called the glycocalyx ( 7 ).The biomaterials destined for degradation are delivered to lysosomes through endocytic/phagocytic and autophagic pathways ( Fig. 1 ). Endocytosis or phagocytosis of extracellular particles or plasma membrane proteins begins with the invagination of the plasma membrane to form endocytic vesicles, which then undergo a series of maturation processes to fi rst become early endosomes, and then late endosomes [excellently reviewed in ( 5 )] ( Fig. 1 ). In the late endosomes, the destined-to-be-degraded cargo is sorted into the intraluminal vesicles via the endosomal sorting complexes required for transport system ( 5 ). Intraluminal Abstract Lysosomes are acidic compartments in mammalian cells that are primarily responsible for the breakdown of endocytic and autophagic substrates such as membranes, proteins, and lipids into their basic building blocks. Lysosomal storage diseases (LSDs) are a group of metabolic disorders caused by genetic mutations in lysosomal hydrolases required for catabolic degradation, mutations in lysosomal membrane proteins important for catabolite export or membrane traffi cking, or mutations in nonlysosomal proteins indirectly affecting these lysosomal functions. A hallmark feature of LSDs is the primary and secondary excessive accumulation of undigested lipids in the lysosome, which causes lysosomal dysfunction and cell death, and subsequently pathological symptoms in various tissues and organs. There are more than 60 types of LSDs, but an effective therapeutic strategy is still lacking for most of them. Several recent in vitro and in vivo studies suggest that induction of lysosomal exocytosis could effectively reduce the accumulation of the storage materials. Meanwhile, the molecular machinery and regulatory mechanisms for lysosomal exocytosis are beginning to be revealed. In this paper, we fi rst discuss these recent developments with the focus on the functional interactions between lipid storage and lysosomal exocytosis. We th...

show abstract

Calcium Triggers Exocytosis from Two Types of Organelles in a Single Astrocyte

Cited by 87 publications

References 62 publications

Injured astrocytes are repaired by Synaptotagmin XI-regulated lysosome exocytosis

Injured astrocytes are repaired by Synaptotagmin XI-regulated lysosome exocytosis

SLC17A9 Protein Functions as a Lysosomal ATP Transporter and Regulates Cell Viability

Lysosomal exocytosis and lipid storage disorders

Contact Info

Product

Resources

About