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

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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 1 2005

ASJC Scopus subject areas

  • Medicine(all)

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    Asanuma, K., Kim, K., Oh, J., Giardino, L., Chabanis, S., Faul, C., Reiser, J., & Mundel, P. (2005). Synaptopodin regulates the actin-bundling activity of α-actinin in an isoform-specific manner. Journal of Clinical Investigation, 115(5), 1188-1198. https://doi.org/10.1172/JCI200523371