The ability of cells to export proteins is essential for numerous cellular functions. Proteins for export are synthesised in the endoplasmic reticulum (ER) and move through the Golgi complex to the trans-Golgi network (TGN), from where they are shipped to various final destinations including the plasma membrane (PM) (apical or basolateral, in polarized cells), early and late endosomes, and secretory granules. The membranous carriers involved in the trafficking step from the TGN directly to the PM are much larger than vesicles, and are pleiomorphic rather than vesicular. They also do not possess an external coat, as has been seen with other types of carriers (e.g. clathrin, COPI and COPII vesicles). At present, the molecular mechanisms of the formation of these large pleiomorphic carriers are completely unknown. I built up a thematic interactome to look at interactions between the many players involved in TGN-to-PM trafficking, and I have added some newly discovered interesting interactions through use of a two-hybrid matrix system. I thus focused my attention on some key elements such as the Arf1 and Arl1 interacting protein Arfaptin, the TRAnsport Protein Particle (TRAPP) complex, protein kinase D (PKD) and C-terminal binding protein/VBFA-ribosylated substrate (Ctbpl-S/BARS) since these were revealed as being important nodes into this thematic interactome. Arfaptin is a protein specifically recruited to the TGN through a BAR domain which can interact with membranes, possibly bending them; thus Arfaptin might be relevant in the initial formation of carriers. We have discovered that PKD (a protein involved in fission) phosphorylates and displaces Arfaptin from the Golgi complex, regulating its action in time, since the fission-mediated action of PKD occurs later.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:500605 |
| Date | January 2009 |
| Creators | Gaibisso, Renato |
| Publisher | Open University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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