Abstract

The extracellular levels of lysosomal enzymes have been implicated in the development of uncontrolled cellular growth, tumor invasiveness, and the inflammatory response. Previous work in our laboratory has uncovered a mannosyl/glucosyl-specific receptor system associated with macrophage plasma membranes which mediates adsorptive pinocytosis (uptake) of lysosomal glycosidases and glycoproteins having mannose in the terminal position. The receptor also recognizes glucose and N-acetylglycosamine but not galactose. We are studying the mode and mechanism of uptake of lysosomal enzymes by macrophages. To accomplish this we have developed methods to fractionate macrophages by Percoll gradient sedimentation and to follow the uptake of ligands by electron microscopy. We have identified an intracellular compartment in macrophages which appears to mediate separation of receptor-ligand complexes and recycling of free receptors to the cell surface. The regulation of the receptor will be studied by following ligand binding and by preparing receptor-specific antibody. The interrelationships between ligand and internalization and lysosomal enzyme biosynthesis and turnover are being investigated. (E)

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM042259-20
Application #
3300768
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1978-12-01
Project End
1993-11-30
Budget Start
1990-12-05
Budget End
1991-11-30
Support Year
20
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130

  Publications

Chen, Pin-I; Kong, Chen; Su, Xiong et al. (2009) Rab5 isoforms differentially regulate the trafficking and degradation of epidermal growth factor receptors. J Biol Chem 284:30328-38
Stahl, Philip D; Wainszelbaum, Marisa J (2009) Human-specific genes may offer a unique window into human cell signaling. Sci Signal 2:pe59
Smith, Jill; Su, Xiong; El-Maghrabi, Raafat et al. (2008) Opposite regulation of CD36 ubiquitination by fatty acids and insulin: effects on fatty acid uptake. J Biol Chem 283:13578-85
Wainszelbaum, Marisa J; Charron, Audra J; Kong, Chen et al. (2008) The hominoid-specific oncogene TBC1D3 activates Ras and modulates epidermal growth factor receptor signaling and trafficking. J Biol Chem 283:13233-42
Su, Xiong; Kong, Chen; Stahl, Philip D (2007) GAPex-5 mediates ubiquitination, trafficking, and degradation of epidermal growth factor receptor. J Biol Chem 282:21278-84
Kong, Chen; Su, Xiong; Chen, Pin-I et al. (2007) Rin1 interacts with signal-transducing adaptor molecule (STAM) and mediates epidermal growth factor receptor trafficking and degradation. J Biol Chem 282:15294-301
Wainszelbaum, Marisa J; Proctor, Brandon M; Pontow, Suzanne E et al. (2006) IL4/PGE2 induction of an enlarged early endosomal compartment in mouse macrophages is Rab5-dependent. Exp Cell Res 312:2238-51
Magadan, Javier G; Barbieri, M Alejandro; Mesa, Rosana et al. (2006) Rab22a regulates the sorting of transferrin to recycling endosomes. Mol Cell Biol 26:2595-614
Su, Xiong; Lodhi, Irfan J; Saltiel, Alan R et al. (2006) Insulin-stimulated Interaction between insulin receptor substrate 1 and p85alpha and activation of protein kinase B/Akt require Rab5. J Biol Chem 281:27982-90
Barbieri, M A; Ramkumar, T P; Fernadez-Pol, S et al. (2004) Receptor tyrosine kinase signaling and trafficking--paradigms revisited. Curr Top Microbiol Immunol 286:1-20

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