- Insulin-like growth factor 2 receptor
biochemistryand 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.
The structure of the IGF2R is a type I transmembrane protein (that is, it has a single transmembrane domain with its
C-terminuson the cytoplasmic side of lipid membranes) with a large extracellular/lumenal domain and a relatively short cytoplasmic tail Harv|Ghosh|Dahms|Kornfeld|2003. The extracellular domain consists a small region homologous to the collagen-binding domain of fibronectinand of fifteen repeats of approximately 147 amino acidresidues. 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.
IGF2R functions to clear IGF2 from the cell surface to attenuate signalling, and to transport lysosomal
acid hydrolaseprecursors 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 Harv|Ghosh|Dahms|Kornfeld|2003. The IGF2Rs (bound to their cargo) are recognized by the GGAfamily of clathrinadaptor proteins and accumulate in forming clathrin-coated vesicles Harv|Ghosh|Kornfeld|2004. IGF2Rs from both the cell surface and the Golgi are trafficked to the early endosomewhere, in the relatively low pHenvironment 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.
first2 =Nancy H.
title =Mannose 6-phosphate receptors: New twists in the tale
journal =Nature Reviews Molecular and Cell Biology
pmid = 12612639
title =The GGA proteins: key players in protein sorting at the "trans"-Golgi network
journal =European Journal of Cell Biology
pmid = 15511083
Cluster of differentiation
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