NEUROSMLM

The molecular mechanism behind the axonal initial segment diffusion barrier

 Coordinatore KING'S COLLEGE LONDON 

 Organization address address: Strand
city: LONDON
postcode: WC2R 2LS

contact info
Titolo: Mr.
Nome: Paul
Cognome: Labbett
Email: send email
Telefono: +44 207848 8184

 Nazionalità Coordinatore United Kingdom [UK]
 Totale costo 221˙606 €
 EC contributo 221˙606 €
 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-2013-IEF
 Funding Scheme MC-IEF
 Anno di inizio 2014
 Periodo (anno-mese-giorno) 2014-04-01   -   2016-03-31

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    KING'S COLLEGE LONDON

 Organization address address: Strand
city: LONDON
postcode: WC2R 2LS

contact info
Titolo: Mr.
Nome: Paul
Cognome: Labbett
Email: send email
Telefono: +44 207848 8184

UK (LONDON) coordinator 221˙606.40

Mappa


 Word cloud

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membrane    cytoskeleton    axonal    molecular    ais    barrier    organization    axon    generally    single    diffusion    protein    mechanism    ankyring    nanoscopic    polarization    neuronal    molecules   

 Obiettivo del progetto (Objective)

'Polarization is a decisive step in neuronal development and once axonal and somatodendritic domains are generated, they generally persist over the lifetime of an organism. The axonal initial segment (AIS), a stretch of 50 – 100 µm length close to the cell body, bears a specialized cytoskeleton and maintains the polarized distribution of neuronal molecules by blocking the exchange of molecules between axon and soma. The adaptor protein ankyrinG is essential for the assembly of this diffusion barrier and crosslinks ion channels and adhesion molecules to the cytoskeleton. However, the molecular mechanism for the obstruction of molecular diffusion across the AIS remains unclear. Recent insights revealed an ordered arrangement of the cytoskeleton not only in the AIS but also further down the axon, raising the question, how the nanoscopic organization of cytoskeletal molecules in the AIS may directly influence the lateral motion of membrane molecules. Here we aim to use novel single-molecule localization-based superresolution microscopy in primary hippocampal neurons to investigate the molecular architecture of the AIS and to understand the mechanism by which membrane protein diffusion is locally restricted. To do so, we will correlate membrane protein diffusion during neuronal polarization in single cells over time with the nanoscopic organization of the AIS. We hypothesize that a regularly spaced structure based on AnkyrinG specifically reduces membrane mobility in the AIS. Our results will clarify the molecular mechanism that controls the diffusion barrier at the AIS and contribute to our understanding of how neuronal polarity is achieved and more generally, how the membrane cytoskeleton organizes the plasma membrane.'

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