- Licenciado in Biochemistry, 1985, Pontificia Universidad Católica de Chile.
- Biochemist, 1987, Pontificia Universidad Católica de Chile.
- Ph.D., Molecular Biology, 1993, Cornell University, USA.
- Postdoctoral studies, University of Colorado, USA (1993) and University of Alberta, Canada (1997).
All eukaryote cells produce secretion proteins, also known as export proteins, that perfom their functions in the extracellular medium. These proteins are essential for cell communication with their environment and fulfill fundamental roles in the organism. Falling within this category are hormones, neurotransmitters, antibodies, coagulation factors, collagen etc.
The secretion process requires a complex organization of resources and cellular components within specialized compartments that are poorly understood. Our study focuses on two regulatory factors, GBF1 and BIG1/2 proteins. These are responsible for regulating and coordinating the multiple reactions necessary for the correct functioning of the secretory pathway. We have shown that these factors regulate exclusive multiple functions, producing specific movement of proteins exported between different compartments of the secretory pathway.
In collaboration with Dr. María Cecilia Rauch, we are also investigating the role played in protein secretion by the immunosuppressor drugs Tacrolymus and Cyclosporin A. Traditionally these compounds are used to avoid rejection in transplant patients when synthesis of Interleukin B, a mediator hormone of the immune response, decreases. Our work indicates that these compounds also mediate their pharmacological action and their secondary effects through inhibition of GBF1 and/or BIG1/2 function in protein secretion.
- Manolea, F., Claude, A., Chun, J.,Rosas, J and melancon, P. ARF nucleotide exchange factors at the Golgi complex: GBF1 but not BIGs is required for Golgi assembly and function. Journal of Cell Biology. Enviado/en revisión.
- Xinhua Zhao, Alejandro Claude, Justin Chun, David J. Shields, John F. Presley, and Paul Melançon. (2006) GBF1, a cis-Golgi and VTCs-localized ARF-GEF, is implicated in ER-to-Golgi protein traffic. Journal of Cell Science. 119: 3743-3753.
-Claude, A., Zhao, B.P. and Melançon, P. (2003) Characterization of alternatively spliced and truncated forms of the ARF guanine nucleotide exchange factor GBF1 defines regions important for activity. Biochemical Biophysical Research. 303:160-169.
-Claude, A., Zhao, B-P., Kuziemsky, C.E., Dahan, S., Berger, S.J., Yan, J-P., Armold, A.D., Sullivan, E.M. and Melancon, P. (1999) GBF1: A novel Golgi-associated BFA resistant guanine nucleotide exchange factor that displays specificity for ADP-ribosylation factor 5. Journal of Cell Biology. 146:71-84.
-Dominguez, M., Fazel, A., Dahan, S., Lovell, J., Hermo, L., Claude, A., Melancon, P. and Bergeron, J.J.M. (1999) Fragmentation of Golgi cisternae activates the intra Golgi transport assay. Journal of Cell Biology. 145: 673-688.
-Berger, S.J., Claude, A.A. and Melancon, P. (1998) Analysis of recombinant human ADP-ribosylation factors by reversed-phase high-performance liquid chromatography and electrospray mass chromatography. Anal. Biochem. 264(1): 53-65.