Mannose-6-phosphate (M6P) is a molecule bound by
lectin in the
immune system
The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...
. M6P is converted to
fructose 6-phosphate by
mannose phosphate isomerase.
M6P is a key targeting signal for
acid hydrolase precursor proteins that are destined for transport to
lysosome
A lysosome () is a membrane-bound organelle that is found in all mammalian cells, with the exception of red blood cells (erythrocytes). There are normally hundreds of lysosomes in the cytosol, where they function as the cell’s degradation cent ...
s. The M6P tag is added to such proteins in the ''cis''-
Golgi apparatus
The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic Cell (biology), cells. Part of the endomembrane system in the cytoplasm, it protein targeting, packages proteins ...
. Specifically, in a reaction involving
uridine diphosphate (UDP) and
''N''-acetylglucosamine, the enzyme
N-acetylglucosamine-1-phosphate transferase catalyzes the
''N''-linked glycosylation of
asparagine residues with M6P. Once appropriately marked with the M6P targeting signal, these proteins are moved to the ''trans''-Golgi network. There, the M6P
moiety is recognized and bound by
mannose 6-phosphate receptor (MPR) proteins at pH 6.5–6.7.
The M6P-tagged lysosomal enzymes are shipped to the late
endosomes via vesicular transport.
(ERT) for several
lysosomal storage diseases relies on this pathway to efficiently direct synthetic enzymes to the lysosome where each can metabolize its particular substrate.
The pH in the late endosome can reach 6.0, which causes dissociation of M6P from its receptor.
Upon release, the enzymes are ferried to their final destination in the lysosomes.
The MPRs are packed into vesicles that bud off the late endosome and return to the ''trans''-Golgi network.
In this way, the MPRs can be recycled.
See also
*
I-cell disease
*
Insulin-like growth factor 2 receptor
*
Mannose
*
Mannose 1-phosphate
References
External links
*
Role of M6P in protein modification(video)
{{Fructose and galactose metabolic intermediates
Monosaccharide derivatives
Organophosphates