Regulation of trafficking and signalling along the endocytic pathway

Carlos Enrich

Dr. Enrich finished his Bsc. in Biology at the University of Barcelona in 1977 and his Ph.D in Cell Biology at the University of Barcelona in 1983. After completion of his PhD, he worked with Prof. Dr. Carl G.Gahmberg at the department of Biochemistry, University of Helsinki in 1983. From 1986 to 1987, he worked with Dr. W. Howard Evans at the National Institute for Medical Research in London and from 1992 to 1993 he worked with Drs. Richard J. Havel and Keith E. Mostov at the Cardiovascular Research Institute of the University of California, San Francisco (UCSF). In 2005 and 2006, Dr. Enrich worked with Drs. Thomas Grewal and Katharina Gaus of the University of New South Wales in Sydney, Australia. Since October 1997, Dr. Enrich is a full Professor of Cell Biology at the University of Barcelona. From 2002 to 2005, he also served as the Director of the department of Cell Biology and Pathology at the University of Barcelona Faculty of Medicine.

Research summary.
Although cell signalling and endocytic membrane trafficking have traditionally been considered distinct processes, recent studies indicate that endocytic organelles can play a more active role in signal propagation and amplification. Our research group is interested in the regulation of membrane trafficking and signalling along the endocytic compartment. Current studies include the analysis of the morphology and dynamics of early endosomes, the transport of cholesterol from the late endocytic compartment, the caveolin transport and caveolae formation. Two calcium-binding protein have been demonstrated to be involved in those processes but also in the regulation of the Ras/MAPK signalling along the endocytic pathway: calmodulin and annexin A6. Annexin A6-induced alterations in cholesterol transport and inhibition of cPLA2 is linked to caveolin export from the Golgi complex and the formation of caveolae, but also stimulates the membrane recruitment of the Ras regulator, p120GAP, to modulate Ras and Raf-1 activity. Annexin A6 inhibits H-Ras signalling in breast cancer cells. On the other hand, we showed that calmodulin regulates the exit from the early endosomes (towards the late endosomes and recycling pathways) and that a specific cross-talk between calmodulin and PKC organize actin dynamics in the early endosomal compartment thereby regulating the intracellular trafficking of EGF receptor. Finally, we have also studied the trafficking and signalling of K-Ras in the late endosomes, en route to the lysosomal degradation. All these mechanistic and functional relationship between signalling and endocytic compartment are becoming progressively more evident in many different systems.