LRP2
LRP2 (low-density lipoprotein receptor-related protein 2), also known as megalin or gp330, is a multiligand endocytic receptor of the LDL receptor family. It mediates uptake and clearance of lipoproteins, hormones, carrier proteins and morphogens, mainly in absorptive epithelia such as the kidney. Browse Assay Genie's current range of LRP2 research reagents below, or read on for the biology behind the target.
LRP2 is a multiligand endocytic receptor. Working together with CUBN, it mediates endocytosis of high-density lipoproteins, and it takes up polybasic drugs such as aprotinin, aminoglycosides and polymyxin B. In the kidney it drives tubular uptake and clearance of leptin, mediates uptake and lysosomal degradation of CST3 and APOM, and handles 25-hydroxyvitamin D3 bound to GC/DBP, metallothionein-bound heavy metals, selenoprotein SEPP1, survivin (BIRC5), and the MMP2-TIMP1 complex. With CUBN it also mediates renal reabsorption of myoglobin.
The LRP2 protein is a glycoprotein with a large amino-terminal extracellular domain, a single transmembrane domain and a short carboxy-terminal cytoplasmic tail. Its extracellular ligand-binding domains bind diverse macromolecules, including albumin, apolipoproteins B and E, and lipoprotein lipase. It is expressed in many tissues but primarily in absorptive epithelia such as the kidney, and it localises to the apical cell membrane, coated pits and endosomes, as well as to dendrites and axons. Recycling of the receptor is regulated by phosphorylation of its cytoplasmic domain.
LRP2 also has roles in signalling and development. It endocytoses Sonic hedgehog (ShhN) and BMP4, helps localise SHH in the ventral neural tube, and is needed for folate uptake via FOLR1 during neural tube closure. In the adult brain it negatively regulates BMP signalling in the subependymal zone, and in astrocytes it mediates albumin uptake. It is also required for embryonic heart development and normal hearing. Mutations in the LRP2 gene cause Donnai-Barrow syndrome (DBS) and facio-oculoacoustico-renal syndrome (FOAR).
LRP2 mediates tubular reabsorption of proteins, vitamin D complexes, myoglobin and heavy metals in the kidney proximal tubule.
LRP2 controls SHH localisation, BMP4 clearance and folate uptake in the neuroepithelium, and supports neural tube closure and forebrain patterning.
LRP2 transports leptin across the choroid plexus, and its endocytosis in neurons is required for hypothalamic leptin signalling and feeding regulation.
Mutations in LRP2 cause Donnai-Barrow and facio-oculoacoustico-renal syndromes, making it a focus for studies of inherited multisystem disorders.
LRP2 is a multiligand endocytic receptor that internalises lipoproteins, hormones, vitamin-binding proteins, drugs and morphogens such as Sonic hedgehog. It is especially important for protein reabsorption in kidney proximal tubules, and it also contributes to neural development, leptin transport and heart development.
LRP2 is also called megalin and gp330, and DBS is listed as a previous symbol after Donnai-Barrow syndrome. Its earlier name was low density lipoprotein receptor-related protein 2. It belongs to the LDL receptor family, and the gene is a member of the HGNC low density lipoprotein receptors group.
Mouse and rat both have an Lrp2 ortholog, so the receptor can be studied in rodent models. In humans, LRP2 mutations cause Donnai-Barrow syndrome and facio-oculoacoustico-renal syndrome. Check the datasheet of any product for its validated reactivity.
Other LDL receptor-related proteins and associated factors with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P98164; product specifications from Assay Genie datasheets.