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"TANGO1: A guide for proteins transport inside the cell"


Thu, 05/03/2009 - 18:00

"TANGO1: A guide for proteins transport inside the cell"

Researchers from the Centre for Genomic Regulation (CRG) have uncovered a new mechanism for protein secretion in mammalian cell.
The new findings will reveal the mechanism by which bulky (or very big) proteins such as Collagens are secreted from cells and help understand the processes by which cells attach, which is essential for tissue biogenesis.
At least 15% of genes in our genome encode for proteins that are secreted from cells. But, who is in charge of controlling traffic within the cell? Who decides the best travel programme for each newly made protein? What prevents these proteins from travelling to a wrong place? What prevents traffic jams?
Until recently, the general thinking was the proteins destined for secretion were packed into transport carriers without any specific guides or loaders. The transport of proteins is mediated by small containers that form pick cargo (proteins) at the Endoplasmic Reticulum and deliver it to the next station within the cell. This process is repeated and the cargo moves forward and ultimately secreted from cells. But recent evidence suggests that some proteins require special guides for their transport.
The work, published in the prestigious journal Cell, has been directed by Vivek Malhotra, coordinator of the Cell and Developmental Biology Programme at the Centre for Genomic Regulation (CRG) and it reveals the identity of a new protein called, TANGO1 that loads cargo into transport carriers by a novel mechanism.
TANGO1 is in charge of transporting proteins such as collagen VII. Collagen VII is too big to fit in a standard transport carrier. TANGO1 helps in creating a special-big transport carrier for collagen VII but, strangely, employs the same machinery and the same materials used for generating the standard small transport carriers. So it is like uses the same materials but instead of making a small boat, TANGO1 helps in the synthesis of an ocean liner.
TANGO1 captures colagen VII with one end, and holds the transport carrier with its other end and prevents it from leaving the Endoplasmic Reticulum. In this state the transport carrier grows in size to accommodate the bulky collagen VII. Once a transport carrier of a size big enough to accommodate collagen VII is generated, TANGO1 dissociates from collagen VII and from the newly forming mega-transport carrier. The transport carrier is then allowed to depart and travel in the forward direction of secretion. These findings provide strong evidence that cells use specific guides for loading cargo and can make different size carriers depending on the size of cargo.
TANGO1 and skin diseases or metastasis
Upon secretion collagen VII interacts with other adhesive proteins and helps in the attachment of epidermis to the dermis. Patients with genetic defects in collagen VII have a number of severe skin disorders which are collectively called Dystrophic Epidermolysis Bullosa (DEB) and Epidermolysis Bullosa Acquisita (EBA), respectively..TANGO1-mediated collagen VII export could reveal important insights into the process of skin biogenesis.
It is important to note that collagen VII is only secreted by the skin cells and TANGO1 is present in all cells. Malhotra and colleagues suggest that TANGO1 is required for secretion of proteins that are generally required for cell-cell attachment. Cancer cells disrupt the cell-cell attachment and revealing the mechanism of TANGO1 dependent protein secretion of adhesive proteins could help understand cancer metastasis. 
About Vivek Malhotra: Vivek Malhotra is one of world’s leaders on protein secretion and cellular compartmentation. His work is focused on how cellular compartments are made and communicate with each other, and how cells duplicate their compartments during cell division. He has been studying these processes since the late 80s and is acknowledge world wide for his creativity and novel findings.
He obtained his Ph.D from Oxford and was a postdoc at Stanford University. He was a professor at University of California San Diego for 18 years. He joined the Centre for Genomic Regulation, Barcelona as a coordinator of the Cell and Developmental Biology Programme.
The work published on March 6 is the 15th paper by Vivek Malhotra in the Cell journal. 

Reference work: Saito K, Chen M, Bard F, Chen S, Zhou H, Woodley D, Polischuck R, Schekman R and Malhotra V.: “TANGO1 facilitates cargo loading at Endoplasmatic Reticulum exit sites”. Publishing in Cell, March 6 2009, DOI: 10.1016/j.cell.2008.12.025. 

For more information: Laia Cendrós, Communication & PR Dept., Centre for Genomic Regulation (CRG), Dr. Aiguader, 88 – Edif. PRBB, 08003 Barcelona, Spain, Tel. +34 93 316 02 37, e-mail.