Regulation and Molecular Composition of the Golgi-Associated Spectrin Skeleton

Godi, Anna (2002). Regulation and Molecular Composition of the Golgi-Associated Spectrin Skeleton. PhD thesis The Open University.



In spite of the big advances in the identification of the proteins operating in membrane transport to and through the Golgi complex, the mechanisms by which they control the intricacy and dynamics of the Golgi complex are still largely unknown. During the last decade a number of candidates have been identified, including spectrin and ankyrin.
In the present study, the mechanism of spectrin association with Golgi membranes has been investigated. The small GTP-binding protein ARF plays an important role in controlling the assembly of the spectrin skeleton on Golgi membranes. ARF recruits ß-spectrin by stimulating the synthesis of phosphatidylinositol 4,5-bisphosphate (PtdIns4,5P2), to which the spectrin PH domain can bind, and which acts as a regulated docking site for Golgi spectrin.
The increase in PtdIns4,5P2 levels in Golgi membranes represents a novel activity of ARF that is not dependent on the previously-characterised effects of ARF on PLD activity and COPI-coat assembly. This implies the concomitant recruitment to Golgi membranes of a Golgi-specific isoform of phosphatidylinositol 4-kinase, PI4Kbeta, and a still unspecified phosphatidylinositol 4-phosphate 5-kinase (PIP5K).
PMKbeta activity is required for the structural and functional preservation of the Golgi complex since transfection of a kinase-dead PMKbeta markedly alters not just the morphological organisation of the Golgi complex, but also membrane traffic from the Golgi complex to the plasma membrane.
These results indicate that the control of phosphoinositide metabolism by ARF is one of the main mechanisms by which this GTPase controls Golgi complex structure and function, and also identify spectrin as one of the phosphoinositide targets on the Golgi apparatus.

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