Intracellular Cycling of Lysosomal Enzyme Receptors Cytoplasmic Tails' Tales
نویسندگان
چکیده
the TGN and ligand delivery to lysosomes. Deficiencies in both MPRs, or in addition of the mannose 6-phosphate tag, result in massive secretion of lysosome enzyme precursors into the extracellular milieu. In the yeast Saccharomyces cerevisiae, an analogous receptor-mediated pathway transports soluble hy-Los Angeles, California 90095 drolases to the lysosome-like vacuole, although sorting receptors do not appear to reach the cell surface and they recognize peptide sequences in the enzymes rather Lysosomes are acidic, membrane-enclosed organelles than mannose 6-phosphate (reviewed by Conibear and in which endogenous and internalized macromolecules Stevens, 1998). A well characterized example of this are degraded by lumenal hydrolases. The significance pathway involves vacuolar carboxypeptidase Y (CPY), of lysosomes for cellular homeostasis and human dis-and its sorting receptor, the vacuolar protein sorting 10 orders such as I-cell disease has led to extensive research gene product (Vps10p). As with MPRs, deficiencies in on the biogenesis of these organelles. Most soluble hy-Vps10p or in its trafficking result in abnormal secretion drolases reach the lysosome by traversing the secretory of CPY. Vps10p bears no homology to MPRs; however, pathway to the trans Golgi network (TGN), where they it resembles sortilin, a mammalian protein of unknown are sorted from secretory proteins and transported to function that follows a trafficking pathway similar to that endosomes and then lysosomes. This sorting step de-of MPRs (Nielsen et al., 2001). pends on transmembrane receptors that are themselves AP-1 Sorting Function at the TGN: directed through intracellular transport pathways by The Plot Thickens sorting determinants in their cytoplasmic domains (tails). Morphological studies of MPR sorting at the mammalian Characterization of factors that recognize such sorting TGN implicated clathrin-coated structures as the source determinants and guide receptors through their intra-of carriers of MPRs to endosomes (reviewed by Le cellular itineraries is therefore critical to understanding Borgne and Hoflack, 1998). Clathrin-coated vesicles me-lysosome biogenesis. diate traffic between the cell surface, TGN, and endo-The traditional view has been that a heterotetrameric somes. The best characterized components of these protein complex, Adaptor Protein 1 (AP-1), is a key coats are clathrin, which forms the coat's outer lattice, player in sorting lysosomal enzyme receptors at the and AP complexes, which are thought to couple coat TGN. Recent findings, however, suggest reassigning formation to cargo selection by binding clathrin, coat such roles to a novel family of sorting adaptors, the accessory factors, and the tails of transmembrane cargo.
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عنوان ژورنال:
- Cell
دوره 106 شماره
صفحات -
تاریخ انتشار 2001