Insulin-like growth factor 2 receptor
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In biochemistry and cell biology, the insulin-like growth factor 2 receptor (IGF2R), also called the cation-independent mannose-6-phosphate receptor (CI-MPR), is a multifunctional protein receptor that binds insulin-like growth factor 2 (IGF2) at the cell surface and mannose-6-phosphate (M6P)-tagged proteins in the trans-Golgi network.
Structure
The structure of the IGF2R is a type I transmembrane protein (that is, it has a single transmembrane domain with its C-terminus on the cytoplasmic side of lipid membranes) with a large extracellular/lumenal domain and a relatively short cytoplasmic tail (Darby, Dahms & Kornfeld 2003). The extracellular domain consists a small region homologous to the collagen-binding domain of fibronectin and of fifteen repeats of approximately 147 amino acid residues. Each of these repeats is homologous to the 157-residue extracytoplasmic domain of the mannose 6-phosphate receptor. Binding to IGF2 is mediated through one of the repeats, while two different repeats are responsible for binding to mannose-6-phosphate. The IGF2R is approximately 300 kDa in size it appears to exist and function as a dimer.
Function
IGF2R functions to clear IGF2 from the cell surface to attenuate signalling, and to transport lysosomal acid hydrolase precursors from the Golgi apparatus to the lysosome. After binding IGF2 at the cell surface, IGF2Rs accumulate in forming clathrin-coated vesicles and are internalized. In the lumen of the trans-Golgi network, the IGF2R binds M6P-tagged cargo (Ghosh, Dahms & Kornfeld 2003). The IGF2Rs (bound to their cargo) are recognized by the GGA family of clathrin adaptor proteins and accumulate in forming clathrin-coated vesicles (Ghosh & Kornfeld 2004). IGF2Rs from both the cell surface and the Golgi are trafficked to the early endosome where, in the relatively low pH environment of the endosome, the IGF2Rs release their cargo. The IGF2Rs 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 IGF2Rs.
References
- Ghosh, Pradipta; Dahms, Nancy H.; Kornfeld, Stuart (2003), "Mannose 6-phosphate receptors: New twists in the tale", Nature Reviews Molecular and Cell Biology, 4: 203–121, PMID 12612639
- Ghosh, Pradipta; Kornfeld, Stuart (2004), "The GGA proteins: key players in protein sorting at the trans-Golgi network", European Journal of Cell Biology, 83: 257–262, PMID 15511083
See also
Further reading
External links
- Insulin-Like-Growth-Factor+II+Receptor at the U.S. National Library of Medicine Medical Subject Headings (MeSH)