Complete cloning and sequencing of rat gp330/"megalin," a distinctive member of the low density lipoprotein receptor gene family.
- 11 October 1994
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 91 (21), 9725-9729
- https://doi.org/10.1073/pnas.91.21.9725
Abstract
We completed the cDNA cloning and sequencing of gp330, the major kidney glomerular antigen for rat Heymann nephritis. The deduced 4660-aa sequence, expected to constitute a mature protein of M(r) 516,715, consists of a probable N-terminal signal peptide sequence (25 aa), an extracellular region (4400 aa), a single transmembrane domain (22 aa), and a C-terminal cytoplasmic tail (213 aa). The extracellular region contains three types of cysteine-rich repeats characteristic of the low density lipoprotein receptor (LDLR) gene family--36 LDLR ligand-binding repeats forming four clusters of putative ligand-binding domains, 16 growth factor repeats separated by 8 YWTD spacer regions, and 1 C-terminal epidermal growth factor repeat. The cytoplasmic tail contains two copies of the (FX)NPXY motif, which represents a signal for coated pitmediated internalization and an additional similar motif. The overall structure of gp330 is similar to that of the LDLR-related protein (LRP)/alpha 2-macroglobulin receptor and shows even greater similarity to the Caenorhabditis elegans protein, reported as a homologue of LRP. However, gp330 differs from these proteins in (i) the cysteine-rich repeat arrangements found in the extreme extracellular N- and C-terminal regions, (ii) the distribution pattern of cysteine residues in the YWTD spacer regions, (iii) the location of the RX(K/R)R consensus recognition sequence of furin, a precursor processing endoprotease, and (iv) the length and structure of the cytoplasmic tail. We suggest the name megalin (from Greek mega) for gp330, the largest plasma membrane protein identified so far in vertebrates. The cloned cDNA will be useful for studies on the physiological functions of gp330/megalin and for determining its role in Heymann nephritis.Keywords
This publication has 34 references indexed in Scilit:
- A Protein Involved in Calcium Sensing of the Human Parathyroid and Placental Cytotrophoblast Cells Belongs to the LDL-Receptor Protein SuperfamilyExperimental Cell Research, 1994
- STRUCTURES AND FUNCTIONS OF MULTILIGAND LIPOPROTEIN RECEPTORS: Macrophage Scavenger Receptors and LDL Receptor-Related Protein (LRP)Annual Review of Biochemistry, 1994
- Organ distribution in rats of two members of the low-density lipoprotein receptor gene family, gp330 and LRP/alpha 2MR, and the receptor-associated protein (RAP).Journal of Histochemistry & Cytochemistry, 1994
- Renal tubule gp330 is a calcium binding receptor for endocytic uptake of protein.Journal of Histochemistry & Cytochemistry, 1992
- Heymann antigen gp330 demonstrates affinity for fibronectin, laminin, and type I collagen and mediates rat proximal tubule epithelial cell adherence to such matrices in vitroExperimental Cell Research, 1990
- Initial events in the formation of immune deposits in passive Heymann nephritis. gp330-anti-gp330 immune complexes form in epithelial coated pits and rapidly become attached to the glomerular basement membrane.The Journal of Experimental Medicine, 1987
- Monoclonal antibodies with exclusive reactivity against parathyroid cells and tubule cells of the kidney.Proceedings of the National Academy of Sciences of the United States of America, 1987
- Single-Step Method of RNA Isolation by Acid Guanidinium Thiocyanate–Phenol–Chloroform ExtractionAnalytical Biochemistry, 1987
- The human LDL receptor: A cysteine-rich protein with multiple Alu sequences in its mRNACell, 1984
- Immunocytochemical localization of the Heymann nephritis antigen (GP330) in glomerular epithelial cells of normal Lewis ratsThe Journal of Experimental Medicine, 1983