title: Synaptopodin regulates the actin-bundling activity of alpha-actinin in an isoform-specific manner.
abstract: Synaptopodin is the founding member of a novel class of proline-rich actin-associated proteins highly expressed in telencephalic dendrites and renal podocytes. Synaptopodin-deficient (synpo(-/-)) mice lack the dendritic spine apparatus and display impaired activity-dependent long-term synaptic plasticity. In contrast, the ultrastructure of podocytes in synpo(-/-) mice is normal. Here we show that synpo(-/-) mice display impaired recovery from protamine sulfate-induced podocyte foot process (FP) effacement and LPS-induced nephrotic syndrome. Similarly, synpo(-/-) podocytes show impaired actin filament reformation in vitro. We further demonstrate that synaptopodin exists in 3 isoforms, neuronal Synpo-short (685 AA), renal Synpo-long (903 AA), and Synpo-T (181 AA). The C terminus of Synpo-long is identical to that of Synpo-T. All 3 isoforms specifically interact with alpha-actinin and elongate alpha-actinin-induced actin filaments. synpo(-/-) mice lack Synpo-short and Synpo-long expression but show an upregulation of Synpo-T protein expression in podocytes, though not in the brain. Gene silencing of Synpo-T abrogates stress-fiber formation in synpo(-/-) podocytes, demonstrating that Synpo-T serves as a backup for Synpo-long in synpo(-/-) podocytes. In concert, synaptopodin regulates the actin-bundling activity of alpha-actinin in highly dynamic cell compartments, such as podocyte FPs and the dendritic spine apparatus.
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, New York, New York, USA.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Asanuma
authors.forename: Kwanghee
authors.initials: K
authors.lastname: Kim
authors.forename: Jun
authors.initials: J
authors.lastname: Oh
authors.forename: Laura
authors.initials: L
authors.lastname: Giardino
authors.forename: Sophie
authors.initials: S
authors.lastname: Chabanis
authors.forename: Christian
authors.initials: C
authors.lastname: Faul
authors.forename: Jochen
authors.initials: J
authors.lastname: Reiser
authors.forename: Peter
authors.initials: P
authors.lastname: Mundel
mesh_terms: D000185:Actinin / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D051379:Mice; D008840:Microfilament Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008854:Microscopy, Electron; D020033:Protein Isoforms / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D008840:Microfilament Proteins; D020033:Protein Isoforms; C503968:Synpo protein, mouse; D000185:Actinin