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PMID: 19196245 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Out, in and back again: PtdIns(4,5)P(2) regulates cadherin trafficking in epithelial morphogenesis.

The Biochemical journal ·Vol. 418 ·No. 2 ·2009-03-01 ·Pages 247-60

Schill NJ, Anderson RA

Abstract

The morphogenesis of epithelial cells in the tissue microenvironment depends on the regulation of the forces and structures that keep cells in contact with their neighbours. The formation of cell-cell contacts is integral to the establishment and maintenance of epithelial morphogenesis. In epithelial tissues, the misregulation of the signalling pathways that control epithelial polarization induces migratory and invasive cellular phenotypes. Many cellular processes influence cadherin targeting and function, including exocytosis, endocytosis and recycling. However, the localized generation of the lipid messenger PtdIns(4,5)P(2) is emerging as a fundamental signal controlling all of these processes. The PtdIns(4,5)P(2)-generating enzymes, PIPKs (phosphatidylinositol phosphate kinases) are therefore integral to these pathways. By the spatial and temporal targeting of PIPKs via the actions of its functional protein associates, PtdIns(4,5)P(2) is generated at discrete cellular locales to provide the cadherin-trafficking machinery with its required lipid messenger. In the present review, we discuss the involvement of PtdIns(4,5)P(2) and the PIPKs in the regulation of the E-cadherin (epithelial cadherin) exocytic and endocytic machinery, the modulation of actin structures at sites of adhesion, and the direction of cellular pathways which determine the fate of E-cadherin and cell-cell junctions. Recent work is also described that has defined phosphoinositide-mediated E-cadherin regulatory pathways by the use of organismal models.

MeSH Terms
Actins/metabolism,physiology Animals Cadherins/metabolism Cell Membrane/metabolism Cell Polarity/physiology Epithelium/drug effects,embryology,metabolism Exocytosis/physiology Humans Intercellular Junctions/metabolism,physiology Metabolic Networks and Pathways/physiology Models, Biological Morphogenesis/drug effects,physiology Phosphatidylinositol 4,5-Diphosphate Phosphatidylinositol Phosphates/pharmacology,physiology Phosphatidylinositols/metabolism,physiology Protein Transport/drug effects,physiology
Chemicals
Actins Cadherins Phosphatidylinositol 4,5-Diphosphate Phosphatidylinositol Phosphates Phosphatidylinositols
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Schill Nicholas J
Program in Cellular and Molecular Biology, University of Wisconsin, Madison, WI 53706, USA.
Anderson Richard A
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
1470-8728
DOI
10.1042/BJ20081844
Published
2009-03-01
Pages
247-60
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC3740165
Subset
IM
Grants
NCI NIH HHS · R01 CA104708 · United States
NCI NIH HHS · R01CA104708 · United States
NIGMS NIH HHS · R01GM057549 · United States
NIGMS NIH HHS · R01 GM057549 · United States
NIGMS NIH HHS · R01 GM114386 · United States
External Links
PubMed source DOI: 10.1042/BJ20081844 PMC Full Text View journal details
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