Award details

Molecular and cellular analysis of the interaction between centaurin-alpha1 and a novel kinesin protein

ReferenceBB/C515455/1
Principal Investigator / Supervisor Professor Venkateswarlu Kanamarlapudi
Co-Investigators /
Co-Supervisors
Institution University of Bristol
DepartmentPharmacology
Funding typeResearch
Value (£) 224,600
StatusCompleted
TypeResearch Grant
Start date 01/09/2005
End date 31/05/2007
Duration21 months

Abstract

By switching between an inactive GDP- and an active GTP-bound form, ADP-ribosylation factor (ARF)6 regulates membrane trafficking and actin dynamics, which are, together, involved in diverse cellular functions including cell adhesion and movement. The formation of inactive ARF-GDP is stimulated by a phosphoinositide 3,4,5-trisphosphate (PIP3)-binding centaurin-a1 GTPase activating protein (GAP). Consistent with the activity as an ARF6 regulator, centaurin-a1 affects membrane trafficking and actin dynamics by contributing to the site-specific regulation of ARF6 (Venkateswarlu et al [2004] J.Biol. Chem. 279:6205). It does so by recruiting itself to specific intracellular locations via binding to lipids and proteins. We have recently isolated a novel kinesin motor protein, KIF13B, as a centaurin-a1 interactor by yeast two-hybrid screening. Centaurin-a1, through its GAP domain, directly interacts with the stalk domain of KIF13B and this interaction is essential in order to maintain centaurin-a1 localisation at the leading edges of the cell. Moreover, KIF13B regulates ARF6 GAP activity of centaurin-a1 in vivo. The objective of this proposal is to test the hypothesis that the centaurin-a1-KIF13B interaction is important for the intracellular trafficking of ARF6 and/or PIP3 and the interaction is regulated by phosphorylation. The specific aims described above will address this hypothesis.

Summary

unavailable
Committee Closed Committee - Biochemistry & Cell Biology (BCB)
Research TopicsX – not assigned to a current Research Topic
Research PriorityX – Research Priority information not available
Research Initiative X - not in an Initiative
Funding SchemeX – not Funded via a specific Funding Scheme
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