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Proteins exiting the cell: How to go where you are expected?


Dm, 17/05/2011 - 19:01

Proteins exiting the cell: How to go where you are expected?

Researchers from the Centre for Genomic Regulation (CRG) have uncovered a new mechanism for the sorting of secretory proteins in mammalian cells.

The findings, which are published in the Developmental Cell journal, reveal a new molecular mechanism for the sorting of secretory proteins at the Golgi apparatus. These secreted proteins include for example insulin, neurotransmitters, hormones, antibodies and components of the extracellular matrix. This process is therefore of fundamental importance for the normal function of the cell.
Proteins are required within and outside the cell and it is therefore essential that all proteins are delivered to the right place. It is well known that proteins destined to some specific cellular compartments as well as proteins exiting the cell are transported through the Secretory Pathway. However, it remains unclear how these proteins are properly sorted to their final destination.
CRG researchers, from the Intracellular Compartmentation laboratory, have previously reported in the Journal of Cell Biology in 2010 the role of actin, a protein of the cytoskeleton, in the sorting of secretory proteins. They now reveal further insight into this process and describe in a new article, in the Developmental Cell journal, the involvement of actin in maintaining a proper balance of Calcium at the main sorting station of the Secretory Pathway, the trans-Golgi Network (TGN).
Since secretory proteins are very diverse and have various fates, it has long been thought that they would all be sorted to their final destination with the help of specific receptors, of which only one has been identified at the TGN after decades of research. “The most exciting part of our findings is that we describe a very novel mechanism, which does not involve specific receptors. We realized that the Calcium concentration of the trans-Golgi Network is crucial for the proper sorting of a set of soluble secretory proteins” explains Julia von Blume, first author of this work. “It is a subtle balance that is maintained by the interaction of the actin cytoskeleton, a family of actin remodelling proteins and a Calcium ion transporter at the membrane of the trans-Golgi Network. If this balance is perturbed, a large number of secretory proteins are sorted randomly, and do not reach their destination”.
“These findings provide the means to understand the sorting of proteins and will help understand the pathologies such as diabetes, asthma, skin and bone morphogenesis”, add the main authors of this work Julia von Blume, Anne-Marie Alleaume and Vivek Malhotra.
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 and ICREA Research Professor.
Reference work: Julia von Blume, Anne-Marie Alleaume, Gerard Cantero-Recasens, Amy Curwin, Timo Zimermann, Amado Carreras-Sureda, Josse van Galen, Yuichi Wakana, Miguel Ángel Valverde and Vivek Malhotra: “ADF/Cofilin regulates the secretory cargo sorting at the TGN via the Ca2+ ATPase SPCA1”. Publishing in Developmental Cell, May 17 2011.
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.