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SHR Neuro Cancer Cardio Metab Microb Lipid

GASP and post-endocytic trafficking of virally encoded chemokine receptors

Abstract: A number of human and animal herpes (HHV4-8) and pox viruses encode G -protein coupled receptors
(GPCRs) with seven transmembrane (7TM) segments - most of which are clearly related to human chemokine
receptors. It appears, that these receptors are used by the virus for either immune evasion, cellular transformation,
tissue targeting, and possibly for cell entry. In addition, many virally-encoded chemokine 7TM/GPCRs have been
suggested to be causally involved in pathogenic phenotypes like Kaposi sarcoma, atherosclerosis and HIVinfection.
However, to date, the role of these receptors during the viral life cycle and in viral pathogenesis is poorly
understood. The majority of these receptors is found in the membranes of intracellular organelles that include
components of the endocytotic pathway, i.e. multivesicular endosomes/lysosomes. It was suggested that this is the
place where the viral receptors are incorporated into the viral membranes during the final stages virus assembly.
Here, we set out to elucidate the mechanisms by which these viral receptors are endocytosed and targeted
to these intracellular lysosomal compartments. One protein has recently been identified that specifically targets
7TM/GPCRs - typically by interaction with their carboxy-terminal domains to the degradative pathways. This
protein is the GPCR-associated sorting protein GASP. By addressing the post-endocytic trafficking properties of
these viral receptors and their possible interaction with GASP, we hope to gain important insights in the function
and pathology of these viral proteins.

Keywords: medical molecular biology; cell biology / cytology; virology; Adaptor proteins; Chemokines; G protein coupled receptors; Herpesvirus; Post-endocytic trafficking

Project Leader:: Waldhoer Maria

Duration:: 01.04.2006-31.03.2011

Programme:: Einzelprojekt

Type of Research: basic research

Staff: Waldhoer, Maria, Project Leader

MUG Research Units: Division of Pharmacology

Project partners: Medizinische Universität Wien (MUW), Austria
Contact person: Prof. Michael Freissmuth;

Funded by: FWF, Fonds zur Förderung der Wissenschaftlichen Forschung, Wien, Austria

Project results published: > The cannabinoid receptor CB1 modulates the signali... J Biol Chem. 2012; 287(53):44234-44248; > D-type prostanoid receptor enhances the signaling ... J Allergy Clin Immunol. 2012; 129(2): 500.e1- 500.e9; > Human cytomegalovirus-encoded UL33 and UL78 hetero... Blood. 2012; 119(21):4908-4918; > Heteromerization of human cytomegalovirus encoded ... Biochem Pharmacol. 2011; 82(6):610-619; > GPR55 ligands promote receptor coupling to multipl... BRIT J PHARMACOL. 2010; 160(3): 604-614.; > Prostaglandin H2 induces the migration of human eo... J Leukoc Biol. 2009; 85(1): 136-145.; > Structure, function and physiological consequences... Br J Pharmacol. 2008; 153 Suppl 1(3): S154-S166.