Disease relevance of GM2AP

• In this paper, we describe the overexpression of GM2AP in Sf21 cells using both the baculovirus expression vector system (BEVS) and a non-lytic, plasmid-based insect cell expression system (InsectSelect) [1].

High impact information on GM2AP

• We conclude that a mannose-6-phosphate-independent pathway for the lysosomal delivery of GM2AP exists in cultured human keratinocytes [2].
• Interestingly, even nonglycosylated GM2AP is delivered to the lysosome, as shown by tunicamycin treatment and subcellular fractionation [2].
• The processing, intracellular transport, and endocytosis of the GM2 activator protein (GM2AP), an essential cofactor of beta-hexosaminidase A for the degradation of ganglioside GM2, was investigated in human epidermal keratinocytes [2].
• The GM2AP precursor is synthesized as an 18-kDa peptide, which is singly glycosylated, resulting in 22-kDa high mannose and 24-27-kDa complex glycoforms [2].
• To investigate the structural basis of phospholipid binding further, GM2AP was cocrystallized with phosphatidylcholine (PC), known to interact with GM2AP [3].

Biological context of GM2AP

• In addition, a fluorescence resonance energy transfer (FRET)-based assay system showed that these variants had the same capacity as wild-type GM2AP for intervesicular lipid transfer from donor to acceptor liposomes [4].
• Also, its endocytosis is independent of carbohydrate-linked signals and is even more effective for nonglycosylated GM2AP [2].
• In addition, and contrary to data on the human GM2AP, the nematode homologue does not inhibit platelet activating factor-induced calcium mobilisation in neutrophils, but actually enhances mediator-induced chemotaxis [5].

Anatomical context of GM2AP

• GM2-activator protein (GM2AP) is a lysosomal lipid transfer protein with important biological roles in ganglioside catabolism, phospholipid metabolism, and T-cell activation [3].

Associations of GM2AP with chemical compounds

• Previous studies of crystal structures of GM2AP complexed with the physiological ligand GM2 and platelet activating factor (PAF) have shown binding at two specific locations within the spacious apolar pocket and an ordering effect of endogenous resident lipids [3].

Other interactions of GM2AP

• The parasite GM2AP does not facilitate degradation of GM2 ganglioside by N-acetyl-beta-hexosaminidase A, although it does inhibit phospholipase D activity [5].

Analytical, diagnostic and therapeutic context of GM2AP

• Study of interaction of GM2 activator protein with GM2 using circular dichroism and fluorescence spectroscopy [6].
• As it was shown by immunoblot analysis of the cell culture supernatant, in both expression systems the GM2AP precursor protein was efficiently secreted into the medium [1].

References