Actin cytoskeleton remodeling governs aquaporin-4 localization in astrocytes.
Aquaporin-4 (AQP4) is constitutively concentrated in the plasma membrane of the perivascular glial processes, and its expression is altered in certain pathological conditions associated with brain edema or altered glial migration. When astrocytes are grown in culture, they lose their characteristic star-like shape and AQP4 continuous plasma membrane localization observed in vivo. In this study, we differentiated primary astrocyte cultures with cAMP and lovastatin, both able to induce glial stellation through a reorganization of F-actin cytoskeleton, and obtained AQP4 selectively localized on the cell plasma membrane associated with an increase in the plasma membrane water transport level, but only cAMP induced an increase in AQP4 total protein expression. Phosphorylation experiments indicated that AQP4 in astrocytes is neither phosphorylated nor a substrate of PKA. Depolymerization of F-actin cytoskeleton performed by cytochalasin-D suggested that F-actin cytoskeleton plays a primary role for AQP4 plasma membrane localization and during cell adhesion. Finally, AQP4 knockdown does not compromise the ability of astrocytes to stellate in the presence of cAMP, indicating that astrocyte stellation is independent of AQP4.
Nicchia
Grazia Paola
GP
Department of General and Environmental Physiology, Centre of Excellence in Comparative Genomics (CEGBA), University of Bari, Bari, Italy. p.nicchia@biologia.uniba.it
Rossi
Andrea
A
Mola
Maria Grazia
MG
Procino
Giuseppe
G
Frigeri
Antonio
A
Svelto
Maria
M
D008841:Actin Cytoskeleton / Q000378:metabolism* / Q000648:ultrastructure; D000199:Actins / Q000378:metabolism; D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics / Q000378:metabolism*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D048430:Cell Shape / Q000187:drug effects / Q000502:physiology; D022081:Cell Surface Extensions / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism / Q000648:ultrastructure*; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D015536:Down-Regulation / Q000235:genetics; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D008148:Lovastatin / Q000494:pharmacology; D051379:Mice; D034622:RNA Interference; D051381:Rats
D000199:Actins; D051401:Aquaporin 4; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin; D000242:Cyclic AMP