Author/Editor		Stenovec, Matjaž; Trkov, Saša; Smolič, Tina; Kreft, Marko; Parpura, Vladimir; Zorec, Robert
Title		Presenilin PS1 [delta]E9 disrupts mobility of secretory organelles in rat astrocytes
Type		članek
Publication year		2018
Volume		str. str.
ISSN		1748-1716 - Acta physiologica (Oxford, England)
Language		eng
Abstract		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.
Keywords		astrocytes presenilin 1 regulated exocytosis astrociti presenilin 1 regulirana eksocitoza