Role of the P-Rex family in neuronal plasticity
Lead Research Organisation:
Babraham Institute
Department Name: UNLISTED
Abstract
Synaptic plasticity is a complex adaptation of nerve cells to how and how much they are used, and therefore it forms an important part of the process of learning. To date, over 120 molecules have been found to play a role in regulating synaptic plasticity. Recently, it has emerged that small G proteins of the Rho-family are key players among these molecules. One type of neuron that displayes synaptic plasticity is the Purkinje neuron of the cerebellum. This project tests the hypothesis that P-Rex family enzymes, regulators of Rho-family G proteins, are involved in the control of Purkinje neuron plasticity. The project ties in with TB group's research on the role of astrocytes in neuronal plasticity and with HW group's work on the role of the P-Rex family in neuronal differentiation, intracellular signalling and mouse motor behaviour.
People |
ORCID iD |
| Heidi Christine Welch (Principal Investigator) |
Publications
Lindsay CR
(2011)
P-Rex1 is required for efficient melanoblast migration and melanoma metastasis.
in Nature communications
Lawson CD
(2011)
P-Rex1 and Vav1 cooperate in the regulation of formyl-methionyl-leucyl-phenylalanine-dependent neutrophil responses.
in Journal of immunology (Baltimore, Md. : 1950)
Donald S
(2008)
P-Rex2 regulates Purkinje cell dendrite morphology and motor coordination.
in Proceedings of the National Academy of Sciences of the United States of America
Dai Y
(2011)
Ca2+-dependent monomer and dimer formation switches CAPRI Protein between Ras GTPase-activating protein (GAP) and RapGAP activities.
in The Journal of biological chemistry
Barber MA
(2012)
The guanine-nucleotide-exchange factor P-Rex1 is activated by protein phosphatase 1a.
in The Biochemical journal
Aslan JE
(2011)
Characterization of the Rac guanine nucleotide exchange factor P-Rex1 in platelets.
in Journal of molecular signaling
| Description | This project has established the role of the P-Rex family in neuronal plasticity. We showed that P-Rex1 and P-Rex2 are required for the maintenance of long-term cerebellar plasticity. |
| Exploitation Route | Our findings have been taken forward by several other labs worldwide who have shown, among other findings, that P-Rex1 is important in autism. |
| Sectors | Education,Healthcare |
| URL | http://www.babraham.ac.uk/our-research/signalling/heidi-welch |
| Description | Other labs have followed up our study to show that P-Rex1 is important for neuronal function and that P-Rex1 deficient mice show autistic behaviors. A recent study has shown that P-Rex1 levels are dowregulated in autistic human individuals. |
| First Year Of Impact | 2015 |
| Sector | Education,Healthcare,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Societal,Economic |
| Title | Collection of P-Rex-deficient and control tissues. |
| Description | This is available to interested research groups, mainly for testing of panels of new P-Rex antibodies. |
| Type Of Material | Biological samples |
| Year Produced | 2006 |
| Provided To Others? | Yes |
| Impact | Better characterised research tools for the P-Rex research field. |
| Title | Role of P-Rex in cancer metastasis |
| Description | Our P-Rex deficeint mice crossed with mouse models of cancer metastasis |
| Type Of Material | Model of mechanisms or symptoms - non-mammalian in vivo |
| Year Produced | 2006 |
| Provided To Others? | Yes |
| Impact | Provides the field with the research tools to investigate a role for P-Rex in metastasis formation |
| Title | Role of P-Rex in motor coordination |
| Description | P-Rex deficient mice in behaviour testing and electrophysiological experiments showed that P-Rex controls motor coordination. |
| Type Of Material | Model of mechanisms or symptoms - mammalian in vivo |
| Year Produced | 2007 |
| Provided To Others? | Yes |
| Impact | Publication currently submitted, further collaborations envisaged. |
| Description | Alexander Zarbock (Uni Muenster, Germany) |
| Organisation | University of Münster |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | Role of P-Rex1 in neutrophil rolling and adhesion |
| Collaborator Contribution | exchange of reagents joint paper |
| Impact | joint paper |
| Start Year | 2008 |
| Description | Marcus Thelen (IRB, Bellinzona, Switzerland) |
| Organisation | Institute for Research in Biomedicine (IRB) |
| Country | Spain |
| Sector | Academic/University |
| PI Contribution | Marcus is interested in P-Rex activation through phosphorylation within cytokine signalling pathways. We've collaborated for many years, on a succession of project. |
| Collaborator Contribution | exchange of reagents, lab visits, joint experiment, joint publication |
| Impact | joint publications production of mAB 6F12 |
| Description | Role of P-Rex in synaptic plasticity |
| Organisation | Babraham Institute |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We provided genetically modified mouse strains with an intruiging phenotype, and a publication describing them that formed the basis of this collaboration. |
| Collaborator Contribution | New avenue of research for our lab. Successful project. Joint manuscript submitted |
| Impact | A joint manuscript has been published in 2010 in PLOS One. |
| Start Year | 2007 |