project . 2011 - 2014 . Closed

LRRK2 modulation of Wnt signalling cascades in Parkinson's disease.

Wellcome Trust
  • Funder: Wellcome TrustProject code: 095010
  • Funded under: Neuroscience and Mental Health Funder Contribution: 243,216 GBP
  • Status: Closed
  • Start Date
    01 Nov 2011
    End Date
    30 Nov 2014
Description
Mutations in PARK8, encoding LRRK2, are the most frequent known cause of Parkinson's disease. LRRK2 is a cytosolic protein kinase that harbours a Roc-COR tandem domain with intrinsic GTPase activity. Modification of LRRK2 GTPase and kinase activity by familial PD mutations in the Roc, COR and kinase domains leads to neuronal death, but the pathways involved remain elusive. We have uncovered compelling evidence that LRRK2 interacts with dishevelled (DVL) family phosphoproteins (DVL1-3), key regul ators of Wnt signalling pathways, and have shown that pathogenic mutations affecting the LRRK2 RocCOR tandem domain modulate interactions with DVLs. We now demonstrate t...
Description
Mutations in PARK8, encoding LRRK2, are the most frequent known cause of Parkinson's disease. LRRK2 is a cytosolic protein kinase that harbours a Roc-COR tandem domain with intrinsic GTPase activity. Modification of LRRK2 GTPase and kinase activity by familial PD mutations in the Roc, COR and kinase domains leads to neuronal death, but the pathways involved remain elusive. We have uncovered compelling evidence that LRRK2 interacts with dishevelled (DVL) family phosphoproteins (DVL1-3), key regul ators of Wnt signalling pathways, and have shown that pathogenic mutations affecting the LRRK2 RocCOR tandem domain modulate interactions with DVLs. We now demonstrate t...
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