Differential expression of the lysosome-associated membrane proteins in normal human tissues.
The lysosome-associated membrane proteins LAMP-1 and LAMP-2 have closely related structures, with 37% sequence homology, and are major constituents of the lysosomal membrane. Their roles are unknown, but they are thought to be structural or functional components of the lysosomal membrane. Recent reports suggest that despite their similar structure and common localization, LAMP-1 and LAMP-2 may have different functions. In our further study of these two molecules, the presence of LAMP-1 and LAMP-2 in a variety of human tissues was analyzed by immunohistochemistry, and their localization was compared to that of cathepsin D, a lysosomal hydrolase. the tissue content of LAMP-1 and LAMP-2 and their respective mRNAs were also analyzed by Northern and Western blotting. The LAMP molecules were detected by immunohistochemistry primarily in metabolically active cells, with a cytoplasmic distribution similar to that of cathepsin D and consistent with their predominant localization in lysosomes. However, there were marked differences in the intensity of staining and, in some cases, the localization of the three proteins. For example, there was much stronger staining for LAMP-2 than LAMP-1 in brain tissue and prostate ductal cells. These differences in localization were consistent with the results obtained in Western blotting of protein extracted from the tissues. The pattern of mRNA expression was similar in all of the examined tissues, with a single mRNA identified for LAMP-1 and two splice variant forms seen for LAMP-2. Our studies of these molecules in human tissues support the conclusion that the expression of the molecules is independently controlled in some tissues, suggesting that the molecules may have independent as well as similar functions.
Furuta
K
K
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA.
Yang
X L
XL
Chen
J S
JS
Hamilton
S R
SR
August
J T
JT
D015703:Antigens, CD / Q000302:isolation & purification*; D015152:Blotting, Northern; D015153:Blotting, Western; D002402:Cathepsin D / Q000302:isolation & purification; D002460:Cell Line; D015342:DNA Probes; D006801:Humans; D007150:Immunohistochemistry; D051907:Lysosomal Membrane Proteins; D008247:Lysosomes / Q000737:chemistry*; D008562:Membrane Glycoproteins / Q000302:isolation & purification*; D014018:Tissue Distribution
D015703:Antigens, CD; D015342:DNA Probes; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D002402:Cathepsin D