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Presenilin PS1 [delta]E9 disrupts mobility of secretory organelles in rat astrocytes [Elektronski vir]Stenovec, Matjaž ...Aim Alzheimer's disease (AD) is largely considered a neuron-derived insult, but also involves failure of astroglia. A recent study indicated that mutated presenilin 1 (PS1M146V), a putative ... endoplasmic reticulum (ER) Ca2+ channel with decreased Ca2+ conductance, impairs the traffic of astroglial peptidergic vesicles. Whether other pathogenically relevant PS1 mutants, such as PS1[delta]E9, which code for ER channel with putative increased Ca2+ conductance, similarly affect vesicle traffic, is unknown. Methods Here, we cotransfected rat astrocytes with plasmids encoding mutant PS1[delta]E9 and atrial natriuretic peptide or vesicular glutamate transporter 1 tagged with fluorescent proteins (pANP.emd or pVGLUT1-EGFP respectively), to microscopically examine whether alterations in vesicle mobility and Ca2+-regulated release of gliosignalling molecules manifest as a general vesicle-based defect; control cells were transfected to co-express exogenous or native wild-type PS1 and pANP.emd or pVGLUT1-EGFP. The vesicle mobility was analysed at rest and after ATP stimulation that increased intracellular calcium activity. Results In PS1[delta]E9 astrocytes, spontaneous mobility of both vesicle types was reduced (P < .001) when compared to controls. Post-stimulatory recovery of fast vesicle mobility was hampered in PS1[delta]E9 astrocytes. The ATP-evoked peptide release was less efficient in PS1[delta]E9 astrocytes than in the controls (P < .05), as was the pre-stimulatory mobility of these vesicles. Conclusion Although the PS1 mutants PS1M146V and PS1[delta]E9 differently affect ER Ca2+ conductance, our results revealed a common, vesicle-type indiscriminate trafficking defect in PS1[delta]E9 astrocytes, indicating that reduced secretory vesicle-based signalling is a general deficit in AD astrocytes.Source: Acta physiologica [Elektronski vir]. - ISSN 1748-1716 (Vol. 223, iss.2, Jun. 2018, str. 1-12)Type of material - e-article ; adult, seriousPublish date - 2018Language - englishCOBISS.SI-ID - 33634009
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Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Stenovec, Matjaž | 15467 |
Trkov, Saša | 31572 |
Smolič, Tina, biologinja | 39164 |
Kreft, Marko | 15666 |
Parpura, Vladimir | ![]() |
Zorec, Robert, 1958- | 03702 |
Source: Personal bibliographies
and: SICRIS
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