Abstract
The Rho family of small GTPases (RhoA, Rac1 and Cdc42) controls signal-transduction pathways that influence many aspects of cell behaviour, including cytoskeletal dynamics. At the leading edge, Rac1 and Cdc42 promote cell motility through the formation of lamellipodia and filopodia, respectively. On the contrary, RhoA promotes the formation of contractile actin-myosin-containing stress fibres in the cell body and at the rear. Here, we identify synaptopodin, an actin-associated protein, as a novel regulator of RhoA signalling and cell migration in kidney podocytes. We show that synaptopodin induces stress fibres by competitive blocking of Smurf1-mediated ubiquitination of RhoA, thereby preventing the targeting of RhoA for proteasomal degradation. Gene silencing of synaptopodin in kidney podocytes causes the loss of stress fibres and the formation of aberrant non-polarized filopodia and impairment of cell migration. Together, these data show that synaptopodin is essential for the integrity of the podocyte actin cytoskeleton and for the regulation of podocyte cell migration.
| Original language | English |
|---|---|
| Pages (from-to) | 485-491 |
| Number of pages | 7 |
| Journal | Nature cell biology. |
| Volume | 8 |
| Issue number | 5 |
| State | Published - May 1 2006 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cell Biology
Cite this
Synaptopodin orchestrates actin organization and cell motility via regulation of RhoA signalling. / Asanuma, Katsuhiko; Yanagida-Asanuma, Etsuko; Faul, Christian H; Tomino, Yasuhiko; Kim, Kwanghee; Mundel, Peter.
In: Nature cell biology., Vol. 8, No. 5, 01.05.2006, p. 485-491.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Synaptopodin orchestrates actin organization and cell motility via regulation of RhoA signalling.
AU - Asanuma, Katsuhiko
AU - Yanagida-Asanuma, Etsuko
AU - Faul, Christian H
AU - Tomino, Yasuhiko
AU - Kim, Kwanghee
AU - Mundel, Peter
PY - 2006/5/1
Y1 - 2006/5/1
N2 - The Rho family of small GTPases (RhoA, Rac1 and Cdc42) controls signal-transduction pathways that influence many aspects of cell behaviour, including cytoskeletal dynamics. At the leading edge, Rac1 and Cdc42 promote cell motility through the formation of lamellipodia and filopodia, respectively. On the contrary, RhoA promotes the formation of contractile actin-myosin-containing stress fibres in the cell body and at the rear. Here, we identify synaptopodin, an actin-associated protein, as a novel regulator of RhoA signalling and cell migration in kidney podocytes. We show that synaptopodin induces stress fibres by competitive blocking of Smurf1-mediated ubiquitination of RhoA, thereby preventing the targeting of RhoA for proteasomal degradation. Gene silencing of synaptopodin in kidney podocytes causes the loss of stress fibres and the formation of aberrant non-polarized filopodia and impairment of cell migration. Together, these data show that synaptopodin is essential for the integrity of the podocyte actin cytoskeleton and for the regulation of podocyte cell migration.
AB - The Rho family of small GTPases (RhoA, Rac1 and Cdc42) controls signal-transduction pathways that influence many aspects of cell behaviour, including cytoskeletal dynamics. At the leading edge, Rac1 and Cdc42 promote cell motility through the formation of lamellipodia and filopodia, respectively. On the contrary, RhoA promotes the formation of contractile actin-myosin-containing stress fibres in the cell body and at the rear. Here, we identify synaptopodin, an actin-associated protein, as a novel regulator of RhoA signalling and cell migration in kidney podocytes. We show that synaptopodin induces stress fibres by competitive blocking of Smurf1-mediated ubiquitination of RhoA, thereby preventing the targeting of RhoA for proteasomal degradation. Gene silencing of synaptopodin in kidney podocytes causes the loss of stress fibres and the formation of aberrant non-polarized filopodia and impairment of cell migration. Together, these data show that synaptopodin is essential for the integrity of the podocyte actin cytoskeleton and for the regulation of podocyte cell migration.
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M3 - Article
VL - 8
SP - 485
EP - 491
JO - Nature Cell Biology
JF - Nature Cell Biology
SN - 1465-7392
IS - 5
ER -