Elbediwy, A;
Zhang, Y;
Cobbaut, M;
Riou, P;
Tan, RS;
Roberts, SK;
Tynan, C;
... Parker, PJ; + view all
(2019)
The Rho family GEF FARP2 is activated by aPKC iota to control tight junction formation and polarity.
Journal of Cell Science
, 132
(8)
, Article jcs223743. 10.1242/jcs.223743.
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Abstract
The elaboration of polarity is central to organismal development and to the maintenance of functional epithelia. Among the controls determining polarity are the PAR proteins, PAR6, aPKCι and PAR3, regulating both known and unknown effectors. Here, we identify FARP2 as a ‘RIPR’ motif-dependent partner and substrate of aPKCι that is required for efficient polarisation and junction formation. Binding is conferred by a FERM/FA domain–kinase domain interaction and detachment promoted by aPKCι-dependent phosphorylation. FARP2 is shown to promote GTP loading of Cdc42, which is consistent with it being involved in upstream regulation of the polarising PAR6–aPKCι complex. However, we show that aPKCι acts to promote the localised activity of FARP2 through phosphorylation. We conclude that this aPKCι−FARP2 complex formation acts as a positive feedback control to drive polarisation through aPKCι and other Cdc42 effectors.
| Type: | Article |
|---|---|
| Title: | The Rho family GEF FARP2 is activated by aPKC iota to control tight junction formation and polarity |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1242/jcs.223743 |
| Publisher version: | https://doi.org/10.1242/jcs.223743 |
| Language: | English |
| Additional information: | http://creativecommons.org/licenses/by/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
| Keywords: | Cdc42, FARP, Atypical protein kinase C, Polarity |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10092939 |
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