A novel form of the membrane protein CD147 that contains an extra Ig-like domain and interacts homophilically

Abstract

BackgroundCD147 is a broadly distributed integral membrane glycoprotein with two Ig-like domains implicated in a wide range of functions. It is associated at the cell surface with the monocarboxylate transporters MCT1 and 4 but interactions of the extracellular region have not been characterised.ResultsWe report the characterisation of a form of CD147 with an additional membrane-distal Ig-like domain. In contrast to the two domain form, this three domain form of CD147 interacts homophilically. Surface plasmon resonance analysis using recombinant proteins showed that the interaction was of low affinity (KD ~ 40 μM) and this is typical of many interactions between membrane proteins. cDNA for the 3 domain form are rare but have been identified in human and mouse retina.ConclusionThe finding that the three domain form of CD147 has an extracellular ligand, that is it interacts homophilically, suggests this interaction may be important in aligning lactate transporters in the retina where lactate is an important metabolite.

Basigin-2 Is a Cell Surface Receptor for Soluble Basigin Ligand

“…This result implies that rBSG associates with an unknown membrane receptor prior to being internalized into the cell. Previous reports have suggested that basigin-2 can function as the membrane receptor for soluble basigin protein, but attempts to directly test this hypothesis have not demonstrated this ability (20,31). We tested this hypothesis by repeating the basigin immunoprecipitations from labeled HESC fractions, followed by immunoblotting with neutravidin-HRP to detect the transfer of the biotin label from the SBED-labeled rBSG to basigin-2 in the membrane fraction.…”

“…Together, the evidence suggests that basigin expressed on the surface of cells can function as a counter-receptor for basigin expressed on separate cells or for soluble glycosylated forms of basigin. Nevertheless, previous attempts to demonstrate such a direct interaction between basigin molecules on separate cells or between basigin proteins in solution have not been successful (20,31).…”

“…The molecule is characterized by the presence of two extracellular immunoglobulin-like domains, a single transmembrane domain possessing a charged amino acid, and a short cytoplasmic tail containing a basolateral membrane-targeting motif (21,22). The more recently identified retina-specific isoform of basigin is distinguished by an additional immunoglobulin-like sequence in the extracellular domain of the protein (20,23). According to the current naming system of the National Center for Biotechnology Information, the larger retina-specific isoform has been renamed basigin-1 (accession number NM_001728.2), and the prototypical isoform, possessing two immunoglobulin domains, has been renamed basigin-2 (accession number NM_198589.1).…”

“…Homophilic interactions have been demonstrated for other immunoglobulin superfamily proteins including intercellular adhesion molecules (28), neural cell adhesion molecules (29), and cadherins (30). However, attempts to demonstrate specific homophilic interactions between basigin molecules expressed on separate cells or between soluble forms of recombinant basigin using surface plasmon resonance have not been successful, suggesting that basigin-2 cannot function as a receptor for itself (20,31). To identify possible receptors for soluble basigin ligand, an affinity purification approach was employed.…”

Up‐regulated basigin‐2 in microglia induced by hypoxia promotes retinal angiogenesis

“…Basigin‐2 (NM_198589) is a major isoform of basigin, and it is ubiquitously expressed. While basigin‐1 transcript (NM_001728), with a third immunoglobulin domain (Ig0), is only expressed specifically in the retinal photoreceptors 19, 26, 27. Basigin‐1, associating with a protein secreted from rods, being named as rod‐derived cone viability factor (RdCVF) and glucose transporter (Glut)‐1, form a complex at the cone surface to increase glucose uptake and promotes cone survival 28, 29.…”