Differential localisation of phosphorylated and non-phosphorylated forms of arylsulfatase A in lysosomes

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The phosphohexosyl components of the lysosomal acid hydrolases are believed to form a part of the common recognition marker for the receptor mediated uptake of these glycoproteins by fibroblasts [l-5]. Depending upon the rate of uptake of a particular enzyme by cultured cells, a ‘high uptake’ form may be distinguished from a ‘low uptake’ form of the same enzyme in the same system [6]. The ‘high uptake’ form of /3-glucuronidase [7], which is efficiently and specifically pinocytosed by fibroblasts, is more acidic than the ‘low uptake’ or poorly pinocytosed form; alkaline phosphatase treatment of the former enzyme abolishes its ‘high uptake’ behaviour without diminishing its catalytic activity. Most lysosomal hydrolases are known to exist in two states, the membrane-bound state and the free (non-latent) state [8]. The physiological significance of these two states is poorly understood. Here we show that the phosphorylated high uptake form of arylsulfatase A (arylsulfate sulfohydrolase EC 3.1.6.1) from sheep brain is a membrane-bound enzyme whereas the free non-phosphorylated ‘low uptake’ form is a soluble protein. This is perhaps the first report demonstrating that the high and low uptake forms of a lysosomal enzyme may be correlated with the physiological microenvironments in which these enzymes exist.