Possible role of cortactin phosphorylation by protein kinase Cα in actin-bundle formation at growth cone

Hiroshi Yamada; Tatsuya Kikuchi; Toshio Masumoto; Fan Yan Wei; Tadashi Abe; Tetsuya Takeda; Teiichi Nishiki; Kazuhito Tomizawa; Masami Watanabe; Hideki Matsui; Kohji Takei

doi:10.1111/boc.201500032

Possible role of cortactin phosphorylation by protein kinase Cα in actin-bundle formation at growth cone

Hiroshi Yamada, Tatsuya Kikuchi, Toshio Masumoto, Fan Yan Wei, Tadashi Abe, Tetsuya Takeda, Teiichi Nishiki, Kazuhito Tomizawa, Masami Watanabe, Hideki Matsui, Kohji Takei

IDAC - Division of Aging Science

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

4 Citations (Scopus)

Abstract

Background Information: Cortactin contributes to growth cone morphogenesis by forming with dynamin, ring-shaped complexes that mechanically bundle and stabilise F-actin. However, the regulatory mechanism of cortactin action is poorly understood. Results: Immunofluorescence microscopy revealed that protein kinase C (PKC) α colocalises with cortactin at growth cone filopodia in SH-SY5Y neuroblastoma cells. PKC activation by phorbol 12-myristate 13-acetate causes cortactin phosphorylation, filopodial retraction and F-actin-bundle loss. Moreover, PKCα directly phosphorylates cortactin in vitro at S135/T145/S172, mitigating both cortactin's actin-binding and actin-crosslinking activity, whereas cellular expression of a phosphorylation-mimetic cortactin mutant hinders filopodial formation with a significant decrease of actin bundles. Conclusions: Our results indicate that PKC-mediated cortactin phosphorylation might be implicated in the maintenance of growth cone.

Original language	English
Pages (from-to)	319-330
Number of pages	12
Journal	Biology of the Cell
Volume	107
Issue number	9
DOIs	https://doi.org/10.1111/boc.201500032
Publication status	Published - 2015 Sept 1

Keywords

Actin bundle
Cortactin
Growth cone
Protein kinase C

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10.1111/boc.201500032

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title = "Possible role of cortactin phosphorylation by protein kinase Cα in actin-bundle formation at growth cone",

abstract = "Background Information: Cortactin contributes to growth cone morphogenesis by forming with dynamin, ring-shaped complexes that mechanically bundle and stabilise F-actin. However, the regulatory mechanism of cortactin action is poorly understood. Results: Immunofluorescence microscopy revealed that protein kinase C (PKC) α colocalises with cortactin at growth cone filopodia in SH-SY5Y neuroblastoma cells. PKC activation by phorbol 12-myristate 13-acetate causes cortactin phosphorylation, filopodial retraction and F-actin-bundle loss. Moreover, PKCα directly phosphorylates cortactin in vitro at S135/T145/S172, mitigating both cortactin's actin-binding and actin-crosslinking activity, whereas cellular expression of a phosphorylation-mimetic cortactin mutant hinders filopodial formation with a significant decrease of actin bundles. Conclusions: Our results indicate that PKC-mediated cortactin phosphorylation might be implicated in the maintenance of growth cone.",

keywords = "Actin bundle, Cortactin, Growth cone, Protein kinase C",

author = "Hiroshi Yamada and Tatsuya Kikuchi and Toshio Masumoto and Wei, {Fan Yan} and Tadashi Abe and Tetsuya Takeda and Teiichi Nishiki and Kazuhito Tomizawa and Masami Watanabe and Hideki Matsui and Kohji Takei",

note = "Publisher Copyright: {\textcopyright} 2015 Soci{\'e}t{\'e} Fran{\c c}aise des Microscopies and Soci{\'e}t{\'e} de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.",

year = "2015",

month = sep,

day = "1",

doi = "10.1111/boc.201500032",

language = "English",

volume = "107",

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T1 - Possible role of cortactin phosphorylation by protein kinase Cα in actin-bundle formation at growth cone

AU - Yamada, Hiroshi

AU - Kikuchi, Tatsuya

AU - Masumoto, Toshio

AU - Wei, Fan Yan

AU - Abe, Tadashi

AU - Takeda, Tetsuya

AU - Nishiki, Teiichi

AU - Tomizawa, Kazuhito

AU - Watanabe, Masami

AU - Matsui, Hideki

AU - Takei, Kohji

PY - 2015/9/1

Y1 - 2015/9/1

N2 - Background Information: Cortactin contributes to growth cone morphogenesis by forming with dynamin, ring-shaped complexes that mechanically bundle and stabilise F-actin. However, the regulatory mechanism of cortactin action is poorly understood. Results: Immunofluorescence microscopy revealed that protein kinase C (PKC) α colocalises with cortactin at growth cone filopodia in SH-SY5Y neuroblastoma cells. PKC activation by phorbol 12-myristate 13-acetate causes cortactin phosphorylation, filopodial retraction and F-actin-bundle loss. Moreover, PKCα directly phosphorylates cortactin in vitro at S135/T145/S172, mitigating both cortactin's actin-binding and actin-crosslinking activity, whereas cellular expression of a phosphorylation-mimetic cortactin mutant hinders filopodial formation with a significant decrease of actin bundles. Conclusions: Our results indicate that PKC-mediated cortactin phosphorylation might be implicated in the maintenance of growth cone.

AB - Background Information: Cortactin contributes to growth cone morphogenesis by forming with dynamin, ring-shaped complexes that mechanically bundle and stabilise F-actin. However, the regulatory mechanism of cortactin action is poorly understood. Results: Immunofluorescence microscopy revealed that protein kinase C (PKC) α colocalises with cortactin at growth cone filopodia in SH-SY5Y neuroblastoma cells. PKC activation by phorbol 12-myristate 13-acetate causes cortactin phosphorylation, filopodial retraction and F-actin-bundle loss. Moreover, PKCα directly phosphorylates cortactin in vitro at S135/T145/S172, mitigating both cortactin's actin-binding and actin-crosslinking activity, whereas cellular expression of a phosphorylation-mimetic cortactin mutant hinders filopodial formation with a significant decrease of actin bundles. Conclusions: Our results indicate that PKC-mediated cortactin phosphorylation might be implicated in the maintenance of growth cone.

KW - Actin bundle

KW - Cortactin

KW - Growth cone

KW - Protein kinase C

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Possible role of cortactin phosphorylation by protein kinase Cα in actin-bundle formation at growth cone

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