Biosynthesis and alternate targeting of the lysosomal cysteine protease cathepsin L.
Upregulation of cathepsin L expression, whether during development or cell transformation, or mediated by ectopic expression from a plasmid, alters the targeting of the protease and thus its physiological function. Upregulated procathepsin L is targeted to small dense core vesicles and to the dense cores of multivesicular bodies, as well as to lysosomes and to the plasma membrane for selective secretion. The multivesicular vesicles resemble secretory lysosomes characterized in specialized cell types in that they are endosomes that stably store an upregulated protein and they possess the tetraspanin CD63. Morphologically the multivesicular endosomes also resemble late endosomes, but they store procathepsin L, not the active protease, and they are not the major site for LAMP-1 accumulation. Distinction between the lysosomal proenzyme and active protease thus identifies two populations of multivesicular endosomes in fibroblasts, one a storage compartment and one an enzymatically active compartment. A distinctive targeting pathway using aggregation is utilized to enrich the storage endosomes with a particular lysosomal protease that can potentially activate and be secreted.
Collette
John
J
University of Miami School of Medicine, Department of Molecular and Cellular Pharmacology, Miami, Florida 33101 USA.
Bocock
Jeffrey P
JP
Ahn
Kyujeong
K
Chapman
Richard L
RL
Godbold
Gene
G
Yeyeodu
Susan
S
Erickson
Ann Hart
AH
D000818:Animals; D056668:Cathepsin L; D002403:Cathepsins / Q000096:biosynthesis / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000096:biosynthesis / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism; D004792:Enzyme Precursors / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000201:enzymology*; D021381:Protein Transport / Q000502:physiology; D022161:Transport Vesicles / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology*
D004792:Enzyme Precursors; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L