Synaptopodin regulates the actin-bundling activity of alpha-actinin in an isoform-specific manner
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Synaptopodin regulates the actin-bundling activity of alpha-actinin in an isoform-specific manner. / Asanuma, Katsuhiko; Kim, Kwanghee; Oh, Jun; Giardino, Laura; Chabanis, Sophie; Faul, Christian; Reiser, Jochen; Mundel, Peter.
In: J CLIN INVEST, Vol. 115, No. 5, 05.2005, p. 1188-98.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Synaptopodin regulates the actin-bundling activity of alpha-actinin in an isoform-specific manner
AU - Asanuma, Katsuhiko
AU - Kim, Kwanghee
AU - Oh, Jun
AU - Giardino, Laura
AU - Chabanis, Sophie
AU - Faul, Christian
AU - Reiser, Jochen
AU - Mundel, Peter
PY - 2005/5
Y1 - 2005/5
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 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.
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 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.
KW - Actinin/metabolism
KW - Actins/metabolism
KW - Animals
KW - Brain/metabolism
KW - Kidney/metabolism
KW - Mice
KW - Microfilament Proteins/deficiency
KW - Microscopy, Electron
KW - Protein Isoforms/deficiency
U2 - 10.1172/JCI23371
DO - 10.1172/JCI23371
M3 - SCORING: Journal article
C2 - 15841212
VL - 115
SP - 1188
EP - 1198
JO - J CLIN INVEST
JF - J CLIN INVEST
SN - 0021-9738
IS - 5
ER -