Synaptopodin regulates the actin-bundling activity of α-actinin in an isoform-specific manner

Katsuhiko Asanuma, Kwanghee Kim, Jun Oh, Laura Giardino, Sophie Chabanis, Christian Faul, Jochen Reiser, Peter Mundel

Research output: Contribution to journalArticlepeer-review

233 Scopus citations

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 α-actinin and elongate α-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 α-actinin in highly dynamic cell compartments, such as podocyte FPs and the dendritic spine apparatus.

Original languageEnglish (US)
Pages (from-to)1188-1198
Number of pages11
JournalJournal of Clinical Investigation
Volume115
Issue number5
DOIs
StatePublished - May 2005

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Synaptopodin regulates the actin-bundling activity of α-actinin in an isoform-specific manner'. Together they form a unique fingerprint.

Cite this