Brain-specific interaction of a 91-kDa membrane-bound protein with the cytoplasmic tail of the 300-kDa mannose 6-phosphate receptor

Abstract

The cytoplasmic tail of the 300 kDa mannose 6-phosphate receptor (MPR 300-CT) is thought to play an important role in sorting and targeting of lysosomal enzymes and the insulin-like growth factor II along the biosynthetic and endocytic pathway. In this study a brain specific 91 kDa protein and a 35 kDa protein salt-washed from membranes (referred as TIP 91-M and TIP 35-M) were found to interact with the cytoplasmic receptor tail as assayed by cross-linkage with recombinant [32P] labeled MPR 300-CT. Subcellular fractionation revealed a distinct pattern of distribution of TIP 35-M and TIP 91-M in microsomal and synaptosomal fractions. Furthermore, the formation of cross-link complexes with membrane proteins appeared to be developmentally and regionally regulated in the brain and inhibited upon ATP hydrolysis. The data suggest the requirement of specific protein interactions for MPR 300 functions in neuronal cells.