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.

Publications

10 25 50
 
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 M√ľnster
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