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(Received for publication, May 3, 1996)
From the Mannose 6-phosphate (Man-6-P) is a
posttranslational carbohydrate modification typical of newly
synthesized acid hydrolases that signals targeting from the Golgi
apparatus to the lysosome via Man-6-P receptors (MPRs). Using iodinated
cation independent MPR as a probe in a Western blot assay, we surveyed
levels of Man-6-P glycoproteins in a number of different rat tissues.
Considerable variation was observed with respect to total amounts and
types of Man-6-P glycoproteins in the different tissues. Brain
contained 2-8-fold more Man-6-P glycoproteins than other tissues, with
relative abundance being brain
Volume 271, Number 32,
Issue of August 9, 1996
pp. 19191-19198
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
,
,
,
Center for Advanced Biotechnology and
Medicine, Piscataway, New Jersey 08854, and the
§ Graduate Program of Molecular Biology and Biochemistry and
the 
Department of Pharmacology, University of
Medicine and Dentistry of New Jersey, Piscataway,
New Jersey 08854
testis 
heart > lung kidney ovary spleen > skeletal
muscle liver serum. Analysis of 16 different
lysosomal enzyme activities revealed that brain contains lower
activities than other tissues which suggested that decreased removal of
Man-6-P results in increased levels of Man-6-P glycoproteins. This was
directly demonstrated by comparing activities of phosphorylated
lysosomal enzymes, purified by immobilized MPR affinity chromatography,
with total activities. The phosphorylated forms accounted for a
considerable proportion of the MPR-targeted activities measured in
brain (on average, 36.2%) but very little in lung, kidney, and liver
(on average, 5.5, 2.3, and 0.7%, respectively). Man-6-P glycoproteins
were also isolated from rat brain by MPR affinity chromatography on a
preparative scale. Of the 18 bands resolvable by SDS-polyacrylamide gel
electrophoresis, seven bands were NH2-terminally sequenced
and identified as the known lysosomal enzymes cathepsin L, cathepsin A,
cathepsin D, 
-galactosidase A, arylsulfatase A, and -iduronidase.
One of the major Man-6-P glycoproteins was identified as palmitoyl
protein thioesterase, which was not previously thought to be lysosomal.
This finding raises important questions about the cellular location and
function of palmitoyl protein thioesterase, mutations in which result
in the neurodegenerative disorder, infantile neuronal ceroid
lipofuscinosis.
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