Fingolimod—A sphingosine‐like molecule inhibits vesicle mobility and secretion in astrocytes

Neurons of the vertebrate central nervous system have the capacity to modify synapse number, morphology, and efficacy in response to activity. Some of these functions can be attributed to activity-induced synthesis and secretion of the neurotrophin brain-derived neurotrophic factor (BDNF); however, the molecular mechanisms by which BDNF mediates these events are still not well understood. Using time-lapse confocal analysis, we show that BDNF mobilizes synaptic vesicles at existing synapses, resulting in small clusters of synaptic vesicles “splitting” away from synaptic sites. We demonstrate that BDNF's ability to mobilize synaptic vesicle clusters depends on the dissociation of cadherin–β-catenin adhesion complexes that occurs after tyrosine phosphorylation of β-catenin. Artificially maintaining cadherin–β-catenin complexes in the presence of BDNF abolishes the BDNF-mediated enhancement of synaptic vesicle mobility, as well as the longer-term BDNF-mediated increase in synapse number. Together, this data demonstrates that the disruption of cadherin–β-catenin complexes is an important molecular event through which BDNF increases synapse density in cultured hippocampal neurons.

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Regulation of Peptidergic Vesicle Mobility by Secretagogues

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10.1034/j.1600-0854.2002.31105.x ◽

2002 ◽

Vol 3 (11) ◽

pp. 801-809 ◽

Cited By ~ 5

Author(s):

C. L. Washburn ◽

J. E. Bean ◽

M. A. Silverman ◽

M. J. Pellegrino ◽

P. A. Yates ◽

...

Keyword(s):

Vesicle Mobility

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Regulation of AQP4 surface expression via vesicle mobility in astrocytes

Glia ◽

10.1002/glia.22485 ◽

2013 ◽

Vol 61 (6) ◽

pp. 917-928 ◽

Cited By ~ 48

Author(s):

Maja Potokar ◽

Matjaž Stenovec ◽

Jernej Jorgačevski ◽

Torgeir Holen ◽

Marko Kreft ◽

...

Keyword(s):

Surface Expression ◽

Vesicle Mobility

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Cytoskeleton and Vesicle Mobility in Astrocytes

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10.1111/j.1600-0854.2006.00509.x ◽

2006 ◽

Vol 8 (1) ◽

pp. 12-20 ◽

Cited By ~ 118

Author(s):

Maja Potokar ◽

Marko Kreft ◽

Lizhen Li ◽

J Daniel Andersson ◽

Tina Pangršič ◽

...

Keyword(s):

Vesicle Mobility

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Electrokinetic properties of isolated cerebral-cortex synaptic vesicles

Biochemical Journal ◽

10.1042/bj1360919 ◽

1973 ◽

Vol 136 (4) ◽

pp. 919-926 ◽

Cited By ~ 13

Author(s):

Jack McLaughlin ◽

Kenneth R. Case ◽

H. Bruce Bosmann

Keyword(s):

Cerebral Cortex ◽

Sialic Acid ◽

Ionic Strength ◽

Guinea Pig ◽

Concanavalin A ◽

Synaptic Vesicles ◽

Carboxyl Groups ◽

Electrokinetic Properties ◽

Ph Dependent ◽

Vesicle Mobility

Synaptic vesicles isolated from guinea-pig cerebral cortex had an electrophoretic mobility of −3.55μm·s-1·V-1·cm in saline–sorbitol, pH7.2, at 25°C (ionic strength 0.015g-ions/1). The mobility was pH-dependent, varied with ionic strength and indicated that the vesicular surface contained weak acidic functions with a pKa in the range 3.0–3.8. Although the vesicular surface was determined to be highly negatively charged, treatment with neuraminidase had no effect on mobility and indicated that the relatively strong carboxyl groups of sialic acid do not contribute significantly to vesicular electrokinetic properties. Treatment of synaptic vesicles with trypsin or trypsinized concanavalin A resulted in increases in mobility, but treatment with ribonuclease, deoxyribonuclease, chrondroitinase ABC or hyaluronidase had no significant effect on mobility. Mn2+or Ca2+was more effective in decreasing vesicle mobility than was Mg2+, Sr2+or Ba2+. The electrokinetic properties of the synaptic vesicle surface are discussed and contrasted with the properties of the synaptosomal membrane.

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