THE FAK-ABCA1 SYSTEM

Population context-dependent regulation of membrane lipid composition and downstream activities in mammalian cells: the FAK-ABCA1 system

 Coordinatore UNIVERSITAET ZUERICH 

 Organization address address: Raemistrasse 71
city: ZURICH
postcode: 8006

contact info
Titolo: Prof.
Nome: Lucas
Cognome: Pelkmans
Email: send email
Telefono: +41 44 63 53 123
Fax: +41 44 63 56 830

 Nazionalità Coordinatore Switzerland [CH]
 Totale costo 184˙709 €
 EC contributo 184˙709 €
 Programma FP7-PEOPLE
Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
 Code Call FP7-PEOPLE-2011-IEF
 Funding Scheme MC-IEF
 Anno di inizio 2012
 Periodo (anno-mese-giorno) 2012-11-01   -   2014-10-31

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    UNIVERSITAET ZUERICH

 Organization address address: Raemistrasse 71
city: ZURICH
postcode: 8006

contact info
Titolo: Prof.
Nome: Lucas
Cognome: Pelkmans
Email: send email
Telefono: +41 44 63 53 123
Fax: +41 44 63 56 830

CH (ZURICH) coordinator 184˙709.40

Mappa


 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

populations    activated    golgi    trafficking    cells    membrane    kinase    adhesion    gene    composition    cell    microarray    apparatus    regulation    abca    effect    lipidomic    phosphoproteomic    clathrin    fak    function    independent    characterise    density    microscopy    single    local    focal    endocytosis    signalling    sphingolipid   

 Obiettivo del progetto (Objective)

'The aim of this project is to uncover a novel regulatory mechanism that explains how cells change their membrane lipid composition and trafficking as a function of population context, and how that is used to adapt the cell’s physiology to its microenvironment. To do so, I will use single cell microscopy over large populations, lipidomic, phosphoproteomic and microarray analysis of mice cells deleted from Focal Adhesion Kinase (FAK).

When cells grow at low local cell density or at the edges of cell islets, FAK becomes activated. This event activates signalling and gene regulation. Interestingly, silencing of FAK strongly impairs sphingolipid GM1 amount at the plasma membrane and fate through clathrin-independent endocytosis, leading to drastic diminution of Simian Virus 40 (SV40) infection. Microarray analysis of FAK-KO cells and Wild Type, in dense and sparse contexts, shows that lysosomal, Golgi apparatus and trafficking genes are controlled by activated Focal Adhesion Kinase. ABCA1, a membrane scrambler and cholesterol efflux mediator, is the second overall strongest hit and the only membrane protein amongst the top hits. Strikingly the loss-of-FAK phenotype in cell spreading and growth can be reversed by inhibiting ABCA1, suggesting that FAK act on membranes by controlling ABCA1 production.

I would like to characterise the actors and dynamics of the FAK-ABCA1 system to understand how it couples membrane composition and clathrin-independent trafficking to local environments. I will apply i)phosphoproteomic approach and chromatin Immunoprecipitation for finding key signalling axis from FAK activation to gene regulation, ii)lipidomic for characterizing FAK effect on membrane composition, and iii)leading edge single cell microscopy over large populations both in live or fixed conditions in order to characterise the FAK-ABCA1 system effect on membrane ordering and sphingolipid endocytosis to the Golgi apparatus or lysosome, as a function of cell density'

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