My PhD Research


Tubule formation in the ER was shown by Voeltz et al (2006) to require a class of membrane proteins with unusually short transmembrane (TM) regions. These short TMs are thought to both "wedge" and "scaffold" ER membranes into their tubular architecture. My work demonstrated that a third component, amphipathic helices, is required for tubule formation and that this component is likely to be evolutionarily conserved.

yop1

Assigned TROSY-HSQC spectrum of Yop1p in LMPG:DPPC mixed micelles (q=0.5)

The importance of ER tubules

The tubular ER comprises a highly dynamic, polygonal network of membrane tubules with roles in cell transport, signalling and metabolism. The ratio of sheet ER to tubular ER is cell type dependent. Cells specialised in metabolism such as hepatocytes contain mainly tubules whereas secretory cells (such as pancreatic acinar) contain primarily sheet ER. The composition of the ER can change dramatically during the cell cycle. For example during transition from interphase into mitosis the ER transforms from being primarily tubular to sheet!

conservation

Conservation of amphipathic character amongst Yop1p and Rtn families

ER tubules and disease

Dysfunction of the tubular ER network has been implicated in human diseases such as hereditary spastic paraplegia (HSP) and schizophrenia. In particular proteins involved in the maintanence and dynamics of ER tubules such as Spastin, Atlastin, REEPs and Reticulons have all been implicated in HSP.

topo

Membrane topology of Yop1p


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