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The Extracellular Matrix (ECM) is a fundamental physiological component of all connective tissues in higher eukaryotes, and defects in ECM are linked to many pathological conditions.
The ECM forms through the tightly controlled and regulated secretion of specialised molecules, and collagens are a major secreted component. The coat protein complex II (COPII) mediates the exit from the endoplasmic reticulum (ER) of the majority of proteins, including the basic components of the ECM.

Secretion of collagen precursor molecules (procollagen) into the ECM poses a major challenge for the COPII trafficking machinery, as procollagen assembles in the ER into structures that are much larger than a typical COPII carrier. COPII must drive the formation of “megacarriers”, able to transport procollagen; whilst we are starting to understand how COPII coat flexibility is achieved structurally, the events and factors that drive and regulate the process of megacarrier formation remain largely unknown.

We use biochemical methods and cryo-electron microscopy (cryo-tomography, subtomogram averaging and single particle reconstruction) to understand the interaction of the COPII coat complex with proteins involved in the ER exit of procollagens, such as TANGO1, cTAGE5 and Sedlin, aiming to reveal the molecular basis for exit of procollagen from the ER.


Ongoing projects:

Cryo-electron tomography of assembled coat
Structure of COPII
in complex with regulatory proteins