Molecular and cellular analysis of the interaction between centaurin-alpha1 and a novel kinesin protein
Lead Research Organisation:
Swansea University
Department Name: Institute of Life Science Medical School
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Technical Summary
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.
Organisations
Publications
Chan CHH
(2017)
Shear Stress-Induced Total Blood Trauma in Multiple Species.
in Artificial organs
Davies JC
(2014)
ADP-ribosylation factor 6 regulates endothelin-1-induced lipolysis in adipocytes.
in Biochemical pharmacology
Davies JC
(2014)
Cytohesin 2/ARF6 regulates preadipocyte migration through the activation of ERK1/2.
in Biochemical pharmacology
Eva R
(2017)
EFA6 regulates selective polarised transport and axon regeneration from the axon initial segment.
in Journal of cell science
Eva R
(2012)
ARF6 directs axon transport and traffic of integrins and regulates axon growth in adult DRG neurons.
in The Journal of neuroscience : the official journal of the Society for Neuroscience
Franssen EH
(2015)
Exclusion of integrins from CNS axons is regulated by Arf6 activation and the AIS.
in The Journal of neuroscience : the official journal of the Society for Neuroscience
John DA
(2017)
The Bacterial Species Campylobacter jejuni Induce Diverse Innate Immune Responses in Human and Avian Intestinal Epithelial Cells.
in Frontiers in microbiology
Kalscheuer VM
(2009)
A balanced chromosomal translocation disrupting ARHGEF9 is associated with epilepsy, anxiety, aggression, and mental retardation.
in Human mutation
Kanamarlapudi V
(2016)
Luteinizing hormone/chorionic gonadotrophin receptor overexpressed in granulosa cells from polycystic ovary syndrome ovaries is functionally active.
in Reproductive biomedicine online
Description | Completed some of the objectives described in the proposal in BB/C515455/1. The rest of objectives completed in this grant. |
Exploitation Route | Our findings are useful for better understanding of a fundamental process of life |
Sectors | Pharmaceuticals and Medical Biotechnology |
Description | The findings have been published in high impact journals so that they could be used by other researchers in the same field. |
First Year Of Impact | 2005 |
Sector | Pharmaceuticals and Medical Biotechnology |
Impact Types | Economic |