University of Pittsburgh Department of Biological Sciences presents:
2019 Fall Seminar Series
Dr. JoAnn Trejo
University of California - San Diego
"Cell Signaling by Protease-activated Receptors"
The focus of our research is to delineate the regulatory mechanisms that control signaling by protease-activated receptor-1 (PAR1) and closely-related family members in normal physiology and disease. Our recent efforts have led to the discovery that ubiquitination of PAR1 promotes p38 mitogen-activated protein kinase (MAPK) inflammatory signaling and not lysosomal degradation of the receptor. We also discovered a novel ubiquitin-independent lysosomal pathway for GPCRs. Contrary to conventional view, we found that ubiquitination of certain GPCRs and canonical ubiquitin-binding ESCRTs are not required for receptor lysosomal degradation. We identified ALG-interacting protein (ALIX) and the alpha-arrestin-related domain containing protein-3 (ARRDC3) as key mediators of this GPCR lysosomal sorting pathway. The ALIX/ARRDC3-dependent pathway bypasses the requirement for GPCR ubiquitination and is distinct from the canonical ubiquitin-dependent endosomal sorting complexes required for transport (ESCRT) lysosomal pathway. Moreover, the ALIX/ARRDC3 pathway appears to be dysregulated in cancer. Our central premise is that ubiquitination offers novel and diverse mechanisms for regulation of GPCR biology. Thus, a thorough understanding of the mechanism by which key regulators and mediators of ubiquitination regulate GPCR signaling and trafficking is essential for understanding dysregulated mechanisms in disease and for identifying new drug targets.
Monday, October 7, 2019
169 Crawford Hall
10:50 A.M. refreshments
Host: Dr. Allyson O'Donnell