title: Actin remodeling requires ERM function to facilitate AQP2 apical targeting.
abstract: This study provides the first evidence that actin reorganization during AQP2 vesicular trafficking to the plasma membrane requires the functional involvement of ERM (ezrin/radixin/moesin) proteins cross-linking actin filaments with plasma membrane proteins. We report that forskolin stimulation was associated with a redistribution of moesin from intracellular sites to the cell cortex and with a concomitant enrichment of moesin in the particulate fraction in renal cells. Introduction of a peptide reproducing a short sequence of moesin within the binding site for F-actin induced all the key effects of forskolin stimulation, including a decrease in F-actin, translocation of endogenous moesin, and AQP2 translocation. A straightforward explanation for these effects is the ability of the peptide to uncouple moesin from its putative effector. This modifies the balance between the active and inactive forms of moesin. Extraction with Triton X-100, which preserves cytoskeletal associated proteins, showed that forskolin stimulation or peptide introduction reduced the amount of phophorylated moesin, a molecular modification known to stabilize moesin in an active state. Our data point to a dual role of moesin in AQP2 trafficking: it might modulate actin depolymerization and it participates in the reorganization of F-actin-containing cytoskeletal structures close to the fusion sites of the AQP2-bearing vesicles.
authors.affiliation: Dipartimento di Fisiologia Generale ed Ambientale, University of Bari, Via Amendola 165/A, 70126 Bari, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Tamma
authors.forename: Enno
authors.initials: E
authors.lastname: Klussmann
authors.forename: Johannes
authors.initials: J
authors.lastname: Oehlke
authors.forename: Eberhard
authors.initials: E
authors.lastname: Krause
authors.forename: Walter
authors.initials: W
authors.lastname: Rosenthal
authors.forename: Maria
authors.initials: M
authors.lastname: Svelto
authors.forename: Giovanna
authors.initials: G
authors.lastname: Valenti
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000818:Animals; D051399:Aquaporin 2 / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D016764:Cell Polarity / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology; D008561:Membrane Fusion / Q000502:physiology; D008840:Microfilament Proteins / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D051381:Rats; D022161:Transport Vesicles / Q000378:metabolism
chemical_list: D000199:Actins; D051399:Aquaporin 2; D008840:Microfilament Proteins; D010446:Peptide Fragments; C071058:moesin; D005576:Colforsin