Phosphohexosyl recognition is a general characteristic of pinocytosis of lysosomal glycosidases by human fibroblasts.

Abstract

A B S T R A C T We recently presented data showing that mannose-6-phosphate was a potent competitive inhibitor of pinocytosis of human platelet f8-glucuronidase, and that treatment of "high-uptake" forms of the enzyme with alkaline phosphatase destroyed the high-uptake property of the enzyme without diminishing its catalytic activity. These data indicate that phosphate is a necessary component of the recognition marker on the enzyme for pinocytosis by human fibroblasts, and suggest that the phosphate on highuptake forms of the enzyme is present as a phosphohexosyl moiety. Results presented here show that mannose-6-phosphate is also a potent inhibitor of pinocytosis of the following enzyme preparations: (a)

Coiling phagocytosis of Borrelia burgdorferi by primary human macrophages is controlled by CDC42Hs and Rac1 and involves recruitment of Wiskott-Aldrich Syndrome protein and Arp2/3 complex

“…This is in line with earlier studies wherein localized actin polymerization has been described as the driving force for engulfment in Fc␥R and CR3-mediated phagocytosis (1,20). It has been speculated that the generation of unilateral pseudopods, one of the hallmarks of coiling phagocytosis, may result from asymmetrical clustering of receptors at the microbial attachment site and that this possibly applies to CR3-dependent as well as CR-independent conditions (39).…”

“…On the other hand, uptake via CR3-mediated phagocytosis does not involve substantial extensions of the phagocyte surface, while actin-associated proteins such as the Arp2/3 complex are often found in punctate foci at the respective phagosomes (4,20,28). Coiling phagocytosis of borreliae by macrophages therefore takes a somewhat intermediate position, since spirochetes are engulfed by huge, although unilateral, pseudopods (39), as in Fc␥R-mediated phagocytosis, and yet the nucleating Arp2/ 3 FIG.…”

Mutational Analysis of the Binding Site Residues of the Bovine Cation-dependent Mannose 6-Phosphate Receptor

“…The mannose 6-phosphate receptors (MPRs) 1 function in the specific recognition of phosphorylated mannose residues, which have been identified on numerous proteins, including lysosomal enzymes (1,2), several growth factors (3,4), and a cytokine (5). Although an increasing number of different classes of proteins have been shown to interact with the receptors, the best characterized function of the MPRs in higher eukaryotic cells is their ability to target newly synthesized soluble acid hydrolases to the lysosome (6 -8).…”

Isolation and characterization of a mannan‐binding protein associated with the early chick embryo

“…By comparison with the glycoproteins the mannosaccharides are much less potent possibly reflecting the multivalency of the inhibitory glycoproteins. It is interesting that D-mannosed-phosphate, a potent inhibitor of the uptake of Iysosomal hydrolases by fibroblasts [25] and D-mannose, an inhibitor of the lectin from E. coli [26] were without effect on the agglutinating activity associated with the vitelline membrane. [21] e Calculated using M, 4.7 X 1 04, determined by gel filtration…”