Structural and kinetic basis of evolutionary conserved and divergent microtubule plus end tracking mechanisms

Ziel

In eukaryotic cells the microtubule (MT) cytoskeleton is of crucial importance for many essential cellular functions. The determination of cell morphology, intracellular transport, chromosome segregation in mitosis, and cell motility belong to the processes carried out by MTs. Aberrant cell morphology, developmental diseases and promotion of malignant transformations in animal cells are results of failures in these processes. The dynamically growing plus end of MTs is of special interest as it serves as a cellular hub integrating signals needed to regulate the MT cytoskeleton and its functions. Due to the plus end’s highly dynamic nature and the complexity of protein-protein interactions at the end, it is still unclear which structural transitions take place at microtubule ends and which structures are recognized by regulatory proteins that bind the growing ends selectively. This project aims at a mechanistic understanding of selective targeting of specialized proteins to microtubule ends that exhibit diverse functions there. Two layers of interactions at microtubule ends are addressed in this proposal: (1) We aim to elucidate the molecular origin for the conserved property of end binding proteins (EBs) to bind autonomously to the growing microtubule plus end region, which provides a dynamic platform for second-layer binding of more divergent proteins. (2) We aim to understand the logics underlying the less conserved interactions of these other microtubule associated proteins (MAPs) with EB-decorated MT ends. These two layers of the MT plus-end binding protein interaction network will be analyzed by a concerted, multidisciplinary experimental approach combining in vitro and in vivo experiments, using quantitative fluorescence microscopy to measure the dynamics of MT end tracking and electron microscopy to gain insight into the structural origin of function.

Wissenschaftliches Gebiet

Koordinator

CANCER RESEARCH UK LBG

EU-Beitrag

€ 172 240,80

Adresse

2 Redman Place
E20 1JQ LONDON
Vereinigtes Königreich

Region

London Inner London — West Camden and City of London

Aktivitätstyp

Research Organisations

Kontakt Verwaltung

Holly Elphinstone (Ms.)

Links

Die Organisation kontaktieren Website

Gesamtkosten

Keine Daten

Ziel

Wissenschaftliches Gebiet

Programm/Programme

Thema/Themen

Aufforderung zur Vorschlagseinreichung

Finanzierungsplan

Koordinator

Diese Seite teilen

Herunterladen