Objective
Actin-based motility underlies multiple cellular processes. Polymerisation of actin from the monomeric to the filamentous form is mediated by the Arp2/3 complex. This complex has to be activated to be functional. To date there are two families of proteins that directly bind and activate the Arp2/3 complex through a conserved DDW motif: Wiskott-Aldrich syndrome proteins and cortactin. Initially there was not functional relationship between them until we demonstrated that cortactin binds and activates N-WASP via its SH3 domain. Thus cortactin can activate actin synthesis directly through its N-terminal DDW motif, or indirectly by binding to N-WASP via its c-terminal SH3 domain. Furthermore we demonstrated that cortactin activation of N-WASP is positive/negatively regulated by erk/src phosphorylation of cortactin respectively, probably by regulating the accessibility of its SH3 domain.
Based on these in vitro experiments, we proposed a switch on/off mechanism, which could be an important control mechanism of acti n remodelling. Thus cortactin has emerged as a multidomain protein that acts as a scaffold that redistributes signals to promote Arp2/3 complex mediated actin synthesis in a variety of cellular processes. The major objective of the project is the validation of the model in vivo.
The questions we will try to address are:
1) Cortactin is considered an oncogene. How is the activation state of cortactin contributing to its oncogenic potential?
2) Cortactin redistributes from the cytoplasm to the cortical cytoskeleton. How is the switch affecting its localization? Are there differences in the final actin structure formed? Is it regulating cortactin binding pattern?
3) Cortactin is implicated in pedestal formation by EPEC. Is the switch implicated in pedestal formation or in the underlying diarrhoea? The relevance of translating this model to in vivo settings has already being discussed enthusiastically by the scientist community.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics mutation
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP6-2004-MOBILITY-12
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
IRG - Marie Curie actions-International re-integration grants
Coordinator
MADRID
Spain
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.