High impact information on Scarb2

• First it was shown that a chimeric protein with a Limp II wild-type tail is transported to lysosomes [1].
• These results indicate that the carboxyl-terminal amino acid sequence, including the Leu-Ile motif and the sequence that connects the motif to the transmembrane domain, is critical for the sorting of Limp II to lysosomes [1].
• Lysosomal targeting of Limp II membrane glycoprotein requires a novel Leu-Ile motif at a particular position in its cytoplasmic tail [1].
• Here we show that newly synthesized LGP85 and LGP107 are delivered to late endosomes/lysosomes via a direct route without passing through the cell surface [2].
• These results suggest, therefore, that LGP85 and LGP107 are sorted into distinct transport vesicles at the post-Golgi, presumably the trans-Golgi network (TGN), after which LGP85 is delivered directly to late endosomes/lysosomes, but significant fractions of LGP107 are targeted to early endosomes before transport to late endosomes/lysosomes [2].

Biological context of Scarb2

• The predicted amino acid sequences of LGP85 consisted of 478 amino acid residues (Mr.54,090) and the protein has 11 potential N-glycosylation sites [3].
• Since the NH2 terminal sequence determined from purified LGP85 was identical to the NH2 terminal sequence deduced from the nucleotide sequence of the cDNA, except for the lack of initiator methionine which is likely to be cleaved off posttranslationally, it is likely that LGP85 has an uncleavable signal peptide at the NH2 terminus [3].
• The kinetics of endocytic transport for LGP85 are very similar to those of lamp-1 and lamp-2 [4].

Anatomical context of Scarb2

• Glycine-tyrosine residues (so-called GY motif) which are thought an important signal for delivery of lysosomal membrane glycoproteins to lysosomes were not contained in the cytoplasmic tail of LGP85 (residues 458-478) [3].
• Two lysosomal membrane proteins, LGP85 and LGP107, are delivered to late endosomes/lysosomes through different intracellular routes after exiting from the trans-Golgi network [2].
• Limited and selective localization of the lysosomal membrane glycoproteins LGP85 and LGP96 in rat osteoclasts [5].
• Monospecific antibodies against two major glycoproteins of rat lysosomal membranes with apparent molecular masses of 96 and 85 kDa, termed LGP96 and LGP85, respectively, were used as probes to determine the expression and distribution of lysosomal membranes in rat osteoclasts [5].
• We studied the endocytic transport of an 85-kDa lysosomal membrane glycoprotein (LGP85) from the cell surface to lysosomes in cultured rat hepatocytes [4].

Associations of Scarb2 with chemical compounds

• Hydropathy plots show that LGP85 possesses two strong hydrophobic regions at the NH2 terminus (residues 4-26) and near the COOH terminus (residues 433-457), respectively [3].
• LGP85 appears to be an unique lysosomal membrane glycoprotein that does not require tyrosine residues for targeting to lysosomes [3].
• These vesicles were positive for a lysosomal membrane protein, LGP85, and their formation was inhibited by treatment of the cells with U18666A, which impairs membrane transport out of late endosomal/lysosomal compartments, thereby suggesting that the vesicles are derived from lysosomes [6].
• LGP85 contains about 22.8% carbohydrate and the carbohydrate moiety is composed of mannose, galactose, fucose, glucosamine, galactosamine, and neuraminic acid, in a molar ratio of 40:20:2:23:3:13 [7].
• Sialoglycoprotein with a molecular mass of 85 kDa (LGP85) was purified from rat liver lysosomal membranes with a 0.9% recovery to apparent homogeneity, as determined from the pattern on polyacrylamide gel electrophoresis in the presence and in the absence of SDS [7].

Other interactions of Scarb2

• Interestingly, although LGP107 is delivered from the Golgi to early endosomes containing internalized horseradish peroxidase-conjugated transferrin (HRP-Tfn) en route to lysosomes, LGP85 does not pass through the HRP-Tfn-positive early endosomes [2].

Analytical, diagnostic and therapeutic context of Scarb2

• Here we report two different in vitro analyses (affinity beads and surface plasmon resonance) which revealed specific interaction between the cytoplasmic tail of LGP85 and AP-1 but not so with AP-2 [8].
• Subcellular localization of LGP85 was determined using enzyme immunoassay [7].
• Immunoelectron microscopy clearly confirmed that the localization of LGP85 is mainly confined to lysosomes [7].
• In parallel with the changes in cathepsins, we found that the amounts of LGP120, LGP110, and LGP85, three integral lysosomal membrane proteins, declined significantly after hepatectomy, suggesting that the lysosomal levels are also diminished in regenerating liver [9].
• LGP85 protein and mRNA were detectable in all tissues when analyzed by Western and Northern blotting [10].

References