Lysosomes are the primary site for degradation of normal cellular constituents. Over 30 inheritable """"""""storage diseases"""""""" are caused by specific defects in lysosomal hydrolase activities. Defective lysosomal function is also characteristic of aging and various nutritional disorders. Lysosomal injury during acquired diseases results in extracellular release of activated hydrolase which often produces necrosis and cell death. The mannose 6-phosphate receptor is responsible for localization of many hydrolases in lysosomes. It binds the hydrolases immediately after their synthesis and facilitates their packaging into lysosomes. The receptor also functions on the cell surface to facilitate removal of acid hydrolases from extracellular sites. The long range goal is to determine the molecular basis of mannose 6-phosphate receptor function. Recombinant DNA techniques will be used to introduce structural changes in the receptor, biologic methods will be used to examine their effects on specific aspects of receptor function. The immediate objectives of this proposal, namely to clone a cDNA encoding the mannose 6-phosphate receptor and determine the structure of the receptor, provide the basis for achieving this goal. These studies will contribute to our understanding of lysosome biogenesis, intracellular membrane trafficking and protein sorting.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK036632-02
Application #
3235104
Study Section
Pathobiochemistry Study Section (PBC)
Project Start
1986-01-01
Project End
1988-12-31
Budget Start
1987-01-01
Budget End
1987-12-31
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Tufts University
Department
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02111
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