Astrocyte stellation, a process dependent on Rac1 is sustained by the regulated exocytosis of enlargeosomes.
Bottom Line: Contrary to previous reports, we found stellation to be governed by the small G protein Rac1, up to disappearance of the process when Rac1 was downregulated or blocked by a specific drug.The surface expansion concomitant to cytoskeleton restructuring, also dependent on Rac1, was found to be at least partially sustained by the exocytosis of enlargeosomes, small vesicles distinct from classical cell organelles, which are abundant in astrocytes.Exhaustion of stellation induced by repeated administrations of Y27632 correlated with the decrease of the enlargeosome pool.
Affiliation: Scientific Institute San Raffaele, Division of Neuroscience and IIT Network, Research Unit of Molecular Neuroscience, via Olgettina 58, Milan, Italy.Show MeSH
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Mentions: In flat astrocytes, nocodazol pretreatment (30 μM, 1 h) induced only minor changes. The drug, however, prevented most changes induced by Y27632, that did not go beyond the redistribution of α-actin with appearance of multiple enriched surface sprouts. Outgrowth was limited to a few, thick expansions. Thus, true stellation did not take place (Fig. 2A). The latrunculin A pretreatment (5 μM, 15 min) failed to affect markedly the phenotype of flat astrocytes, including stress fibers. It did however change the effects of Y27632. The shape of latrunculin A/Y27632-treated cells was variable, ranging from flat to stellate. α-Actin distribution was disordered, with formation of scattered clusters protruding from the cell surface (Fig. 2B), while the processes exhibited only few or no surface lamellipodia. Both cytoskeleton-addressed drugs affect therefore stellation, however in different ways. Nocodazol blocks process outgrowth; latrunculin A precludes a correct reorganization of the actin network.
Affiliation: Scientific Institute San Raffaele, Division of Neuroscience and IIT Network, Research Unit of Molecular Neuroscience, via Olgettina 58, Milan, Italy.