The biogenesis of lysosomes

S Kornfeld, I Mellman - Annual review of cell biology, 1989 - annualreviews.org
S Kornfeld, I Mellman
Annual review of cell biology, 1989annualreviews.org
Lysosomes are acidic, hydrolase-rich vacuoles capable of degrading most biological
macromolecules. In spite of this digestive capacity, the acid hydro lases and associated
proteins found in the lysosome's interior, as well as the proteins that comprise the lysosome
membrane, are relatively long-lived. Nevertheless endogenous lysosomal constituents do
turn over and are continuously replaced with newly synthesized components. In addition,
dividing cells must be able to form new lysosomes. During the past several years much has …
Lysosomes are acidic, hydrolase-rich vacuoles capable of degrading most biological macromolecules. In spite of this digestive capacity, the acid hydro lases and associated proteins found in the lysosome's interior, as well as the proteins that comprise the lysosome membrane, are relatively long-lived. Nevertheless endogenous lysosomal constituents do turn over and are continuously replaced with newly synthesized components. In addition, dividing cells must be able to form new lysosomes. During the past several years much has been learned about many aspects of lysosome biogenesis. The selective phosphorylation of mannose residues on lyso somal enzymes, in conjunction with specific receptors for the mannose 6-phosphate recognition marker, is found to be largely responsible for the targeting or" sorting" of newly synthesized lysosomal enzymes. Several lysosomal membrane glycoproteins have been isolated and their structures determined by cDNA cloning. The routing of these various molecules to lysosomes has been studied, and the structural determinants on the pro teins that direct their intracellular trafficking are beginning to be defined. In addition, the organelles involved in mediating the transport of newly synthesized lysosomal enzymes to lysosomes have been generally identified. This information has been derived from a combination of biochemistry, immunocytochemistry, molecular biology, and classical human genetics. The goal of this review is to summarize our current understanding of the biogenesis of lysosomes. The reader is referred to reviews by Robbins (1987) and von Figura and Hasilik (1986) and the recent monograph by Holtzman (1989) for more complete summaries of earlier work.
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