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 H Faul, Jochen Reiser, Peter Mundel

Research output: Contribution to journalArticle

219 Citations (Scopus)

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
Pages (from-to)1188-1198
Number of pages11
JournalJournal of Clinical Investigation
Volume115
Issue number5
DOIs
StatePublished - May 1 2005
Externally publishedYes

Fingerprint

Actinin
Podocytes
Actins
Protein Isoforms
Dendritic Spines
ethylphenylepoxygeranyl ether
Actin Cytoskeleton
Kidney
Telencephalon
Stress Fibers
Neuronal Plasticity
Protamines
Nephrotic Syndrome
Gene Silencing
Dendrites
Proline
Proteins
Up-Regulation
Brain

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Asanuma, K., Kim, K., Oh, J., Giardino, L., Chabanis, S., Faul, C. H., ... 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

Synaptopodin regulates the actin-bundling activity of α-actinin in an isoform-specific manner. / Asanuma, Katsuhiko; Kim, Kwanghee; Oh, Jun; Giardino, Laura; Chabanis, Sophie; Faul, Christian H; Reiser, Jochen; Mundel, Peter.

In: Journal of Clinical Investigation, Vol. 115, No. 5, 01.05.2005, p. 1188-1198.

Research output: Contribution to journalArticle

Asanuma, K, Kim, K, Oh, J, Giardino, L, Chabanis, S, Faul, CH, Reiser, J & Mundel, P 2005, 'Synaptopodin regulates the actin-bundling activity of α-actinin in an isoform-specific manner', Journal of Clinical Investigation, vol. 115, no. 5, pp. 1188-1198. https://doi.org/10.1172/JCI200523371
Asanuma, Katsuhiko ; Kim, Kwanghee ; Oh, Jun ; Giardino, Laura ; Chabanis, Sophie ; Faul, Christian H ; Reiser, Jochen ; Mundel, Peter. / Synaptopodin regulates the actin-bundling activity of α-actinin in an isoform-specific manner. In: Journal of Clinical Investigation. 2005 ; Vol. 115, No. 5. pp. 1188-1198.
@article{d51debb9887e473ab864d00d1b43a590,
title = "Synaptopodin regulates the actin-bundling activity of α-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 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.",
author = "Katsuhiko Asanuma and Kwanghee Kim and Jun Oh and Laura Giardino and Sophie Chabanis and Faul, {Christian H} and Jochen Reiser and Peter Mundel",
year = "2005",
month = "5",
day = "1",
doi = "10.1172/JCI200523371",
language = "English",
volume = "115",
pages = "1188--1198",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "5",

}

TY - JOUR

T1 - Synaptopodin regulates the actin-bundling activity of α-actinin in an isoform-specific manner

AU - Asanuma, Katsuhiko

AU - Kim, Kwanghee

AU - Oh, Jun

AU - Giardino, Laura

AU - Chabanis, Sophie

AU - Faul, Christian H

AU - Reiser, Jochen

AU - Mundel, Peter

PY - 2005/5/1

Y1 - 2005/5/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=18244384042&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=18244384042&partnerID=8YFLogxK

U2 - 10.1172/JCI200523371

DO - 10.1172/JCI200523371

M3 - Article

C2 - 15841212

AN - SCOPUS:18244384042

VL - 115

SP - 1188

EP - 1198

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 5

ER -