An aPKC-Exocyst complex controls paxillin phosphorylation and migration through localised JNK1 activation

Carine Rosse, Etienne Formstecher, Katrina Boeckeler, Yingming Zhao, Joachim Kremerskothen, Michael D. White, Jacques H. Camonis, Peter J. Parker

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

Atypical protein kinase C (aPKC) isoforms have been implicated in cell polarisation and migration through association with Cdc42 and Par6. In distinct migratory models, the Exocyst complex has been shown to be involved in secretory events and migration. By RNA interference (RNAi) we show that the polarised delivery of the Exocyst to the leading edge of migrating NRK cells is dependent upon aPKCs. Reciprocally we demonstrate that aPKC localisation at the leading edge is dependent upon the Exocyst. The basis of this inter-dependence derives from two-hybrid, mass spectrometry, and coimmunoprecipitation studies, which demonstrate the existence of an aPKC-Exocyst interaction mediated by Kibra. Using RNAi and small molecule inhibitors, the aPKCs, Kibra, and the Exocyst are shown to be required for NRK cell migration and it is further demonstrated that they are necessary for the localized activation of JNK at the leading edge. The migration associated control of JNK by aPKCs determines JNK phosphorylation of the plasma membrane substrate Paxillin, but not the phosphorylation of the nuclear JNK substrate, c-jun. This plasma membrane localized JNK cascade serves to control the stability of focal adhesion complexes, regulating migration. The study integrates the polarising behaviour of aPKCs with the pro-migratory properties of the Exocyst complex, defining a higher order complex associated with the localised activation of JNK at the leading edge of migrating cells that determines migration rate.

Original languageEnglish (US)
Article numbere1000235
JournalPLoS Biology
Volume7
Issue number11
DOIs
StatePublished - Nov 2009

Fingerprint

Paxillin
Phosphorylation
protein kinase C
mitogen-activated protein kinase
Cell Movement
phosphorylation
Chemical activation
Cell membranes
RNA Interference
Cell Membrane
RNA
Focal Adhesions
Substrates
RNA interference
cell movement
Mass spectrometry
Mass Spectrometry
Protein Isoforms
plasma membrane
Adhesion

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

Cite this

Rosse, C., Formstecher, E., Boeckeler, K., Zhao, Y., Kremerskothen, J., White, M. D., ... Parker, P. J. (2009). An aPKC-Exocyst complex controls paxillin phosphorylation and migration through localised JNK1 activation. PLoS Biology, 7(11), [e1000235]. https://doi.org/10.1371/journal.pbio.1000235

An aPKC-Exocyst complex controls paxillin phosphorylation and migration through localised JNK1 activation. / Rosse, Carine; Formstecher, Etienne; Boeckeler, Katrina; Zhao, Yingming; Kremerskothen, Joachim; White, Michael D.; Camonis, Jacques H.; Parker, Peter J.

In: PLoS Biology, Vol. 7, No. 11, e1000235, 11.2009.

Research output: Contribution to journalArticle

Rosse, C, Formstecher, E, Boeckeler, K, Zhao, Y, Kremerskothen, J, White, MD, Camonis, JH & Parker, PJ 2009, 'An aPKC-Exocyst complex controls paxillin phosphorylation and migration through localised JNK1 activation', PLoS Biology, vol. 7, no. 11, e1000235. https://doi.org/10.1371/journal.pbio.1000235
Rosse, Carine ; Formstecher, Etienne ; Boeckeler, Katrina ; Zhao, Yingming ; Kremerskothen, Joachim ; White, Michael D. ; Camonis, Jacques H. ; Parker, Peter J. / An aPKC-Exocyst complex controls paxillin phosphorylation and migration through localised JNK1 activation. In: PLoS Biology. 2009 ; Vol. 7, No. 11.
@article{6b3765ff2e914b4b887042ac82ecf0a3,
title = "An aPKC-Exocyst complex controls paxillin phosphorylation and migration through localised JNK1 activation",
abstract = "Atypical protein kinase C (aPKC) isoforms have been implicated in cell polarisation and migration through association with Cdc42 and Par6. In distinct migratory models, the Exocyst complex has been shown to be involved in secretory events and migration. By RNA interference (RNAi) we show that the polarised delivery of the Exocyst to the leading edge of migrating NRK cells is dependent upon aPKCs. Reciprocally we demonstrate that aPKC localisation at the leading edge is dependent upon the Exocyst. The basis of this inter-dependence derives from two-hybrid, mass spectrometry, and coimmunoprecipitation studies, which demonstrate the existence of an aPKC-Exocyst interaction mediated by Kibra. Using RNAi and small molecule inhibitors, the aPKCs, Kibra, and the Exocyst are shown to be required for NRK cell migration and it is further demonstrated that they are necessary for the localized activation of JNK at the leading edge. The migration associated control of JNK by aPKCs determines JNK phosphorylation of the plasma membrane substrate Paxillin, but not the phosphorylation of the nuclear JNK substrate, c-jun. This plasma membrane localized JNK cascade serves to control the stability of focal adhesion complexes, regulating migration. The study integrates the polarising behaviour of aPKCs with the pro-migratory properties of the Exocyst complex, defining a higher order complex associated with the localised activation of JNK at the leading edge of migrating cells that determines migration rate.",
author = "Carine Rosse and Etienne Formstecher and Katrina Boeckeler and Yingming Zhao and Joachim Kremerskothen and White, {Michael D.} and Camonis, {Jacques H.} and Parker, {Peter J.}",
year = "2009",
month = "11",
doi = "10.1371/journal.pbio.1000235",
language = "English (US)",
volume = "7",
journal = "PLoS Biology",
issn = "1544-9173",
publisher = "Public Library of Science",
number = "11",

}

TY - JOUR

T1 - An aPKC-Exocyst complex controls paxillin phosphorylation and migration through localised JNK1 activation

AU - Rosse, Carine

AU - Formstecher, Etienne

AU - Boeckeler, Katrina

AU - Zhao, Yingming

AU - Kremerskothen, Joachim

AU - White, Michael D.

AU - Camonis, Jacques H.

AU - Parker, Peter J.

PY - 2009/11

Y1 - 2009/11

N2 - Atypical protein kinase C (aPKC) isoforms have been implicated in cell polarisation and migration through association with Cdc42 and Par6. In distinct migratory models, the Exocyst complex has been shown to be involved in secretory events and migration. By RNA interference (RNAi) we show that the polarised delivery of the Exocyst to the leading edge of migrating NRK cells is dependent upon aPKCs. Reciprocally we demonstrate that aPKC localisation at the leading edge is dependent upon the Exocyst. The basis of this inter-dependence derives from two-hybrid, mass spectrometry, and coimmunoprecipitation studies, which demonstrate the existence of an aPKC-Exocyst interaction mediated by Kibra. Using RNAi and small molecule inhibitors, the aPKCs, Kibra, and the Exocyst are shown to be required for NRK cell migration and it is further demonstrated that they are necessary for the localized activation of JNK at the leading edge. The migration associated control of JNK by aPKCs determines JNK phosphorylation of the plasma membrane substrate Paxillin, but not the phosphorylation of the nuclear JNK substrate, c-jun. This plasma membrane localized JNK cascade serves to control the stability of focal adhesion complexes, regulating migration. The study integrates the polarising behaviour of aPKCs with the pro-migratory properties of the Exocyst complex, defining a higher order complex associated with the localised activation of JNK at the leading edge of migrating cells that determines migration rate.

AB - Atypical protein kinase C (aPKC) isoforms have been implicated in cell polarisation and migration through association with Cdc42 and Par6. In distinct migratory models, the Exocyst complex has been shown to be involved in secretory events and migration. By RNA interference (RNAi) we show that the polarised delivery of the Exocyst to the leading edge of migrating NRK cells is dependent upon aPKCs. Reciprocally we demonstrate that aPKC localisation at the leading edge is dependent upon the Exocyst. The basis of this inter-dependence derives from two-hybrid, mass spectrometry, and coimmunoprecipitation studies, which demonstrate the existence of an aPKC-Exocyst interaction mediated by Kibra. Using RNAi and small molecule inhibitors, the aPKCs, Kibra, and the Exocyst are shown to be required for NRK cell migration and it is further demonstrated that they are necessary for the localized activation of JNK at the leading edge. The migration associated control of JNK by aPKCs determines JNK phosphorylation of the plasma membrane substrate Paxillin, but not the phosphorylation of the nuclear JNK substrate, c-jun. This plasma membrane localized JNK cascade serves to control the stability of focal adhesion complexes, regulating migration. The study integrates the polarising behaviour of aPKCs with the pro-migratory properties of the Exocyst complex, defining a higher order complex associated with the localised activation of JNK at the leading edge of migrating cells that determines migration rate.

UR - http://www.scopus.com/inward/record.url?scp=72949116594&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=72949116594&partnerID=8YFLogxK

U2 - 10.1371/journal.pbio.1000235

DO - 10.1371/journal.pbio.1000235

M3 - Article

VL - 7

JO - PLoS Biology

JF - PLoS Biology

SN - 1544-9173

IS - 11

M1 - e1000235

ER -