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Pak1 Kinase Maintains Apical Membrane Identity in Epithelia
- Source :
- Cell Reports, Cell Reports, Vol 22, Iss 7, Pp 1639-1646 (2018)
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- Summary Epithelial cells are polarized along their apical-basal axis by the action of the small GTPase Cdc42, which is known to activate the aPKC kinase at the apical domain. However, loss of aPKC kinase activity was reported to have only mild effects on epithelial cell polarity. Here, we show that Cdc42 also activates a second kinase, Pak1, to specify apical domain identity in Drosophila and mammalian epithelia. aPKC and Pak1 phosphorylate an overlapping set of polarity substrates in kinase assays. Inactivating both aPKC kinase activity and the Pak1 kinase leads to a complete loss of epithelial polarity and morphology, with cells losing markers of apical polarization such as Crumbs, Par3/Bazooka, or ZO-1. This function of Pak1 downstream of Cdc42 is distinct from its role in regulating integrins or E-cadherin. Our results define a conserved dual-kinase mechanism for the control of apical membrane identity in epithelia.<br />Graphical Abstract<br />Highlights • aPKC is not the only kinase responsible for epithelial cell polarization in Drosophila • Loss of another Cdc42 effector, Pak1 kinase, causes a moderate polarity phenotype • aPKC and Pak1 kinases act redundantly to maintain apical domain identity • The dual-kinase mechanism of aPKC and Pak1 is conserved in mammalian epithelia<br />Downstream of Cdc42, the atypical protein kinase C (aPKC) is thought to be the main effector at the apical domain. Aguilar-Aragon et al. identify a second kinase, Pak1, as being an additional essential effector downstream of Cdc42 at the apical domain in both Drosophila and mammalian epithelial cells.
- Subjects :
- 0301 basic medicine
CDC42
Article
General Biochemistry, Genetics and Molecular Biology
aPKC
Mice
03 medical and health sciences
PAK1
cancer
Animals
Drosophila Proteins
Humans
Small GTPase
Amino Acid Sequence
Cdc42
Phosphorylation
epithelial polarity
Kinase activity
lcsh:QH301-705.5
development
Protein Kinase C
organoids
ZO-1
Epithelial polarity
Polarity (international relations)
Chemistry
Kinase
Cell Membrane
Cell Polarity
Epithelial Cells
Apical membrane
Cell biology
Drosophila melanogaster
030104 developmental biology
lcsh:Biology (General)
p21-Activated Kinases
Pak1
RNA Interference
Drosophila
Caco-2 Cells
biological
apical domain
Subjects
Details
- ISSN :
- 22111247
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- Cell Reports
- Accession number :
- edsair.doi.dedup.....443a1bc047dd2d2cb13703083982e58f