# BIOCHEMISTRY OF MUCOPOLYSACCHARIDES

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 1988 · $197,344

## Abstract

The long term objective of this research program is to define the
structure, metabolism and function of proteoglycans (mucopolysaccharides)
as these parameters reflect the remodeling of connective tissue in health
and disease.  The research efforts proposed for 6/1/84-5/31/89 will
emphasize studies on the cellular mechanisms involved in the uptake,
intracellular translocation, and secretion of lysosomal enzymes and
proteoglycans.
Major emphasis will continue to be placed on the role of the
phosphomannosyl receptor in the uptake and intracellular transport and
secretion of lysosomal enzymes.  The model system used for these studies
utilizes homogeneous Beta-galactosidase and skin fibroblasts derived from
patients with generalized gangliosidosis (GM1) which lack this lysosomal
enzyme.  Attempts will be made to establsh:  1) how the receptor aggregate
is assembled in the endoplasmic reticulum and/or golgi membranes; 2) the
structural features required for the binding of lysosomal enzymes to the
phosphomannosyl receptor and packaging into lysosomes; 3) how the receptor
is recycled to the golgi and/or the cell surface; and 4) if therapeutic
agents coupled to the phosphomannosyl recognition marker can be efficiently
and specifically targeted to cells and can correct or alleviate abnormal
metabolism (remodeling) of connective tissue.

In parallel studies the mechanism for the uptake of proteoglycans and
proteoglycan derivatives by cells during connective tissue remodeling will
be investigated.  The results of studies in this laboratory provide strong
support for the existence of specific recognition markers and binding
proteins (receptors) for proteoglycans in a number of connective
tissue-associated cell types.  Efforts will be initiated to isolate and
characterize each component of the recognition system.  These studies will
include attempts to establish if the uptake of proteoglycans by cells
represents a simple salvage pathway or possibly participates in the control
of connective tissue remodeling.  Experimentation will be restricted
largely to the binding and uptake of the well-defined protein-chondroitin
4-S04 complex by connective tissue-associated cell types and those in liver.

The above-described studies will involve the use of "state of the art"
tissue culture, radioisotopic, electrophoretic, immunochemical and
cytochemical techniques.

## Key facts

- **NIH application ID:** 3154701
- **Project number:** 5R01AR010531-23
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **SAM.gov UEI:** GNJ7BBP73WE9
- **Principal Investigator:** GEORGE W JOURDIAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $197,344
- **Award type:** 5
- **Project period:** 1979-06-01 → 1989-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3154701

## Citation

> US National Institutes of Health, RePORTER application 3154701, BIOCHEMISTRY OF MUCOPOLYSACCHARIDES (5R01AR010531-23). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3154701. Licensed CC0.

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