Antagonistic regulation of actin dynamics and cell motility by TRPC5 and TRPC6 channels

Dequan Tian; Sarah M.P. Jacobo; David Billing; Anete Rozkalne; Steven D. Gage; Theodora Anagnostou; Hermann Pavenstaedt; Hsiang Hao Hsu; Johannes Schlondorff; Arnolt Ramos; Anna Greka

doi:10.1126/scisignal.2001200

Antagonistic regulation of actin dynamics and cell motility by TRPC5 and TRPC6 channels

Dequan Tian
, Sarah M.P. Jacobo
, David Billing
, Anete Rozkalne
, Steven D. Gage
, Theodora Anagnostou
, Hermann Pavenstaedt
, Hsiang Hao Hsu
, Johannes Schlondorff
, Arnolt Ramos
, Anna Greka^*

^*Corresponding author for this work

Massachusetts General Hospital
University of Münster
Chang Gung Memorial Hospital
Beth Israel Deaconess Medical Center

Research output: Contribution to journal › Journal Article › peer-review

255 Scopus citations

Abstract

The Rho family of small guanosine triphosphatases (Rho GTPases: RhoA, Cdc42, and Rac1) regulates many aspects of cell behavior, including actin dynamics and cell migration. The generation of calcium ion (Ca²⁺) microdomains is critical in promoting cell migration because they control the localized activity of Rho GTPases.We identified receptor-activated TRPC5 and TRPC6 (transient receptor potential canonical type 5 and 6) channels as antagonistic regulators of actin remodeling and cell motility in fibroblasts and kidney podocytes. We show that TRPC5 is in a molecular complex with Rac1, whereas TRPC6 is in a molecular complex with RhoA. TRPC5-mediated Ca ²⁺ influx induces Rac1 activation, thereby promoting cell migration, whereas TRPC6-mediated Ca²⁺ influx increases RhoA activity, thereby inhibiting cell migration. Our data unveil antagonistic Ca²⁺ influx pathways as a conserved signaling mechanism for the integrated regulation of cell migration.

Original language	English
Article number	ra77
Journal	Science Signaling
Volume	3
Issue number	145
DOIs	https://doi.org/10.1126/scisignal.2001200
State	Published - 26 10 2010
Externally published	Yes

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10.1126/scisignal.2001200

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title = "Antagonistic regulation of actin dynamics and cell motility by TRPC5 and TRPC6 channels",

abstract = "The Rho family of small guanosine triphosphatases (Rho GTPases: RhoA, Cdc42, and Rac1) regulates many aspects of cell behavior, including actin dynamics and cell migration. The generation of calcium ion (Ca2+) microdomains is critical in promoting cell migration because they control the localized activity of Rho GTPases.We identified receptor-activated TRPC5 and TRPC6 (transient receptor potential canonical type 5 and 6) channels as antagonistic regulators of actin remodeling and cell motility in fibroblasts and kidney podocytes. We show that TRPC5 is in a molecular complex with Rac1, whereas TRPC6 is in a molecular complex with RhoA. TRPC5-mediated Ca 2+ influx induces Rac1 activation, thereby promoting cell migration, whereas TRPC6-mediated Ca2+ influx increases RhoA activity, thereby inhibiting cell migration. Our data unveil antagonistic Ca2+ influx pathways as a conserved signaling mechanism for the integrated regulation of cell migration.",

author = "Dequan Tian and Jacobo, \{Sarah M.P.\} and David Billing and Anete Rozkalne and Gage, \{Steven D.\} and Theodora Anagnostou and Hermann Pavenstaedt and Hsu, \{Hsiang Hao\} and Johannes Schlondorff and Arnolt Ramos and Anna Greka",

year = "2010",

month = oct,

day = "26",

doi = "10.1126/scisignal.2001200",

language = "英语",

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issn = "1945-0877",

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T1 - Antagonistic regulation of actin dynamics and cell motility by TRPC5 and TRPC6 channels

AU - Tian, Dequan

AU - Jacobo, Sarah M.P.

AU - Billing, David

AU - Rozkalne, Anete

AU - Gage, Steven D.

AU - Anagnostou, Theodora

AU - Pavenstaedt, Hermann

AU - Hsu, Hsiang Hao

AU - Schlondorff, Johannes

AU - Ramos, Arnolt

AU - Greka, Anna

PY - 2010/10/26

Y1 - 2010/10/26

N2 - The Rho family of small guanosine triphosphatases (Rho GTPases: RhoA, Cdc42, and Rac1) regulates many aspects of cell behavior, including actin dynamics and cell migration. The generation of calcium ion (Ca2+) microdomains is critical in promoting cell migration because they control the localized activity of Rho GTPases.We identified receptor-activated TRPC5 and TRPC6 (transient receptor potential canonical type 5 and 6) channels as antagonistic regulators of actin remodeling and cell motility in fibroblasts and kidney podocytes. We show that TRPC5 is in a molecular complex with Rac1, whereas TRPC6 is in a molecular complex with RhoA. TRPC5-mediated Ca 2+ influx induces Rac1 activation, thereby promoting cell migration, whereas TRPC6-mediated Ca2+ influx increases RhoA activity, thereby inhibiting cell migration. Our data unveil antagonistic Ca2+ influx pathways as a conserved signaling mechanism for the integrated regulation of cell migration.

AB - The Rho family of small guanosine triphosphatases (Rho GTPases: RhoA, Cdc42, and Rac1) regulates many aspects of cell behavior, including actin dynamics and cell migration. The generation of calcium ion (Ca2+) microdomains is critical in promoting cell migration because they control the localized activity of Rho GTPases.We identified receptor-activated TRPC5 and TRPC6 (transient receptor potential canonical type 5 and 6) channels as antagonistic regulators of actin remodeling and cell motility in fibroblasts and kidney podocytes. We show that TRPC5 is in a molecular complex with Rac1, whereas TRPC6 is in a molecular complex with RhoA. TRPC5-mediated Ca 2+ influx induces Rac1 activation, thereby promoting cell migration, whereas TRPC6-mediated Ca2+ influx increases RhoA activity, thereby inhibiting cell migration. Our data unveil antagonistic Ca2+ influx pathways as a conserved signaling mechanism for the integrated regulation of cell migration.

UR - https://www.scopus.com/pages/publications/78049524253

U2 - 10.1126/scisignal.2001200

DO - 10.1126/scisignal.2001200

M3 - 文章

C2 - 20978238

AN - SCOPUS:78049524253

SN - 1945-0877

VL - 3

JO - Science Signaling

JF - Science Signaling

IS - 145

M1 - ra77

ER -

Antagonistic regulation of actin dynamics and cell motility by TRPC5 and TRPC6 channels

Abstract

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