Cation-dependent mannose-6-phosphate receptor

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.[5][6]

M6PR
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesM6PR, CD-MPR, MPR 46, MPR-46, MPR46, SMPR, CD-mannose-6-phosphate receptor, cation dependent
External IDsOMIM: 154540 MGI: 96904 HomoloGene: 31086 GeneCards: M6PR
Gene location (Human)
Chr.Chromosome 12 (human)[1]
Band12p13.31Start8,940,361 bp[1]
End8,949,761 bp[1]
Orthologs
SpeciesHumanMouse
Entrez

4074

17113

Ensembl

ENSG00000003056

ENSMUSG00000007458

UniProt

P20645

P24668

RefSeq (mRNA)

NM_001207024
NM_002355

NM_010749

RefSeq (protein)

NP_001193953
NP_002346

NP_034879

Location (UCSC)Chr 12: 8.94 – 8.95 MbChr 6: 122.31 – 122.32 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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 eukaryotes.

Structure

The CD-MPR is a type I transmembrane protein (that is, it has a single transmembrane domain with its C-termini on the cytoplasmic side of lipid membranes) with a relatively short cytoplasmic tail.[7] 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.[7] 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 lectins 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.[7] The MPRs (bound to their cargo) are recognized by the GGA family of clathrin adaptor proteins and accumulate in forming clathrin-coated vesicles.[8] 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.

See also

References

  1. GRCh38: Ensembl release 89: ENSG00000003056 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000007458 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Dahms NM, Lobel P, Breitmeyer J, Chirgwin JM, Kornfeld S (July 1987). "46 kd mannose 6-phosphate receptor: cloning, expression, and homology to the 215 kd mannose 6-phosphate receptor". Cell. 50 (2): 181–92. doi:10.1016/0092-8674(87)90214-5. PMID 2954652. S2CID 23842311.
  6. Pohlmann R, Nagel G, Schmidt B, Stein M, Lorkowski G, Krentler C, Cully J, Meyer HE, Grzeschik KH, Mersmann G (August 1987). "Cloning of a cDNA encoding the human cation-dependent mannose 6-phosphate-specific receptor". Proc. Natl. Acad. Sci. U.S.A. 84 (16): 5575–9. doi:10.1073/pnas.84.16.5575. PMC 298905. PMID 2441386.
  7. Ghosh P, Dahms NM, Kornfeld S (March 2003). "Mannose 6-phosphate receptors: new twists in the tale". Nat. Rev. Mol. Cell Biol. 4 (3): 202–12. doi:10.1038/nrm1050. PMID 12612639. S2CID 16991464.
  8. Ghosh P, Kornfeld S (July 2004). "The GGA proteins: key players in protein sorting at the trans-Golgi network". Eur. J. Cell Biol. 83 (6): 257–62. doi:10.1078/0171-9335-00374. PMID 15511083.

Further reading


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