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Intracellular targeting of inositol 145-trisphosphate receptors

Reference	BB/C005201/1
Principal Investigator / Supervisor	Professor Colin Taylor
Co-Investigators / Co-Supervisors
Institution	University of Cambridge
Department	Pharmacology
Funding type	Research
Value (£)	184,327
Status	Completed
Type	Research Grant
Start date	11/04/2005
End date	10/04/2008
Duration	36 months

Abstract

The spatial and temporal complexity of intracellular Ca signals depends on precise targeting of the proteins responsible for generating and decoding Ca signals. Two families of intracellular Ca channels, ryanodine (RyR) and IP3 receptors (IP3R), are largely responsible for release of Ca from intracellular stores. Our work suggests that each subtype of IP3R and RyR is retained in the ER by similar redundant sequences within the transmembrane domains (TMD). This work aims to define the sequences that target IP3R to ER and the properties of the TMD that retain them in the ER. We aim also to establish the structures within IP3R subtypes that allow selective targeting to different cellular locations and the structures that allow IP3R and RyR to be sent to different organelles. Expression of YFP-tagged IP3R1 fragments/mutants in COS-7 cells will be used to define the ER-targeting and retention sequences. Tagged chimeras will be used to define determinants of selective targeting. IP3R1/3 chimeras for IP3R3 and IP3R1 targeting to near-apical and basolateral membranes of MDCK cells; and IP3R3/RyR1 chimeras IP3R and RyR1 targeting to ER and secretory vesicles in MIN-6 insulinoma cells.

Summary

unavailable

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

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