Cation-dependent mannose-6-phosphate receptor
Encyclopedia
In the fields of biochemistry
and cell biology
, the cation-dependent mannose-6-phosphate receptor (CD-MPR) also known as the 46 kDa mannose 6-phosphate receptor is a protein
that in humans is encoded by the M6PR gene
.
The CD-MPR is one of two transmembrane proteins that bind mannose-6-phosphate
(M6P) tags on acid hydrolase
precursors in the Golgi apparatus
that are destined for transport to the lysosome
. Homologues of CD-MPR are found in all eukaryote
s.
ic side of lipid membrane
s) with a relatively short cytoplasmic tail. The extracytoplasmic/lumenal M6P binding-domain consists of 157 amino acid
residues. The CD-MPR is approximately 46 kDa in size and it both exists and functions as a dimer
.
The cell surface receptor for insulin-like growth factor 2
also functions as a cation-independent mannose 6-phosphate receptor. It consists of fifteen repeats homologous to the 157-residue CD-M6PR domain, two of which are responsible for binding to M6P.
s that bind their M6P-tagged cargo in the lumen
of the Golgi apparatus. The CD-MPR shows greatly enhanced binding to M6P in the presence of divalent
cations, such as manganese
. The MPRs (bound to their cargo) are recognized by the GGA
family of clathrin
adaptor proteins and accumulate in forming clathrin-coated vesicles
. They are trafficked to the early endosome
where, in the relatively low pH
environment of the endosome, the MPRs release their cargo. The MPRs are recycled back to the Golgi, again by way of interaction with GGAs and vesicles. The cargo proteins are then trafficked to the lysosome via the late endosome independently of the MPRs.
Biochemistry
Biochemistry, sometimes called biological chemistry, is the study of chemical processes in living organisms, including, but not limited to, living matter. Biochemistry governs all living organisms and living processes...
and cell biology
Cell biology
Cell biology is a scientific discipline that studies cells – their physiological properties, their structure, the organelles they contain, interactions with their environment, their life cycle, division and death. This is done both on a microscopic and molecular level...
, the cation-dependent mannose-6-phosphate receptor (CD-MPR) also known as the 46 kDa mannose 6-phosphate receptor is a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the M6PR gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
The CD-MPR is one of two transmembrane proteins that bind mannose-6-phosphate
Mannose-6-phosphate
Mannose-6-phosphate is a molecule bound by lectin in the immune system. M6P is converted to fructose 6-phosphate by mannose phosphate isomerase....
(M6P) tags on acid hydrolase
Acid hydrolase
An acid hydrolase is an enzyme that works best at acidic pHs. It is commonly located in lysosomes, which are acidic on the inside. Acid hydrolases may be nucleases, proteases, glycosidases, lipases, phosphatases, sulfatases and phospholipases and make up the approximately 50 degradative enzymes of...
precursors in the Golgi apparatus
Golgi apparatus
The Golgi apparatus is an organelle found in most eukaryotic cells. It was identified in 1898 by the Italian physician Camillo Golgi, after whom the Golgi apparatus is named....
that are destined for transport to the lysosome
Lysosome
thumb|350px|Schematic of typical animal cell, showing subcellular components. [[Organelle]]s: [[nucleoli]] [[cell nucleus|nucleus]] [[ribosomes]] [[vesicle |vesicle]] rough [[endoplasmic reticulum]]...
. Homologues of CD-MPR are found in all eukaryote
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...
s.
Structure
The CD-MPR is a type I transmembrane protein (that is, it has a single transmembrane domain with its C-termini on the cytoplasmCytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
ic side of lipid membrane
Lipid bilayer
The lipid bilayer is a thin membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around cells. The cell membrane of almost all living organisms and many viruses are made of a lipid bilayer, as are the membranes surrounding the cell nucleus...
s) with a relatively short cytoplasmic tail. The extracytoplasmic/lumenal M6P binding-domain consists of 157 amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
residues. The CD-MPR is approximately 46 kDa in size and it both exists and functions as a dimer
Protein dimer
In biochemistry, a dimer is a macromolecular complex formed by two, usually non-covalently bound, macromolecules like proteins or nucleic acids...
.
The cell surface receptor for insulin-like growth factor 2
Insulin-like growth factor 2
Insulin-like growth factor 2 is one of three protein hormones that share structural similarity to insulin.-Gene structure:In humans, the IGF2 gene is located on chromosome 11p15.5, a region which contains numerous imprinted genes. In mice this homologous region is found at distal chromosome 7...
also functions as a cation-independent mannose 6-phosphate receptor. It consists of fifteen repeats homologous to the 157-residue CD-M6PR domain, two of which are responsible for binding to M6P.
Function
Both CD-MPRs and CI-MPRs are lectinLectin
Lectins are sugar-binding proteins that are highly specific for their sugar moieties. They play a role in biological recognition phenomena involving cells and proteins. For example, some viruses use lectins to attach themselves to the cells of the host organism during infection...
s that bind their M6P-tagged cargo in the lumen
Lumen (anatomy)
A lumen in biology is the inside space of a tubular structure, such as an artery or intestine...
of the Golgi apparatus. The CD-MPR shows greatly enhanced binding to M6P in the presence of divalent
Divalent
In chemistry, a divalent ion or molecule has a valence of two and thus can form two bonds with other ions or molecules. An older term for divalent is bivalent....
cations, such as manganese
Manganese
Manganese is a chemical element, designated by the symbol Mn. It has the atomic number 25. It is found as a free element in nature , and in many minerals...
. The MPRs (bound to their cargo) are recognized by the GGA
GGA
GGA or Gga may refer to:*Gereja Generasi Apostolik, Apostolic Generation Church in English*Girl Guides Australia*Good girl art*Goemon's Great Adventure, a 1998 Nintendo 64 video game...
family of clathrin
Clathrin
Clathrin is a protein that plays a major role in the formation of coated vesicles. Clathrin was first isolated and named by Barbara Pearse in 1975. It forms a triskelion shape composed of three clathrin heavy chains and three light chains. When the triskelia interact they form a polyhedral lattice...
adaptor proteins and accumulate in forming clathrin-coated vesicles
Vesicle (biology)
A vesicle is a bubble of liquid within another liquid, a supramolecular assembly made up of many different molecules. More technically, a vesicle is a small membrane-enclosed sack that can store or transport substances. Vesicles can form naturally because of the properties of lipid membranes , or...
. They are trafficked to the early endosome
Endosome
In biology, an endosome is a membrane-bound compartment inside eukaryotic cells. It is a compartment of the endocytic membrane transport pathway from the plasma membrane to the lysosome. Molecules internalized from the plasma membrane can follow this pathway all the way to lysosomes for...
where, in the relatively low pH
PH
In chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...
environment of the endosome, the MPRs release their cargo. The MPRs are recycled back to the Golgi, again by way of interaction with GGAs and vesicles. The cargo proteins are then trafficked to the lysosome via the late endosome independently of the MPRs.