SUPRAMOLECULAR ASSEMBLIES FROM LYSOSOMAL MATRIX PROTEINS AND COMPLEX LIPIDS

Most lysosomal hydrolases are soluble enzymes. Lamp-II (lysosome-assoc iated membrane protein-II) is a major constituent of the lysosomal mem brane. We studied the aggregation of a series of lysosomal molecules. The aggregation-sensitive lysosomal marker enzymes were optimally aggr egated at intralysosomal pH. A similar pH dependence was recorded for aggregation of Lamp-II. The pi-I-dependent loss of solubility of isola ted Lamp-II required components of the lysosome extract. Conditions of mild acid pH promoting aggregation triggered the formation of complex es with lipids of lysosomal origin. We fractionated a membrane-free ly sosome extract by gel-filtration chromatography and could reconstitute assemblies in vitro from separated fractions. We found some selectivi ty in the lysosomal proteins binding to complex lipids, phosphatidylch oline, sphingomyelin, and phosphatidylethanolamine being most effectiv e. We propose that the formation at pH 5.0 of such supramolecular asse mblies between lysosomal proteins and lipids occurs within the intraly sosomal environment. Some possible consequences of such an intralysoso mal matrix formation on organelle function are discussed.