5A11/Basigin Gene Products Are Necessary for Proper Maturation and Function of the Retina

Abstract

5A11/Basigin gene products are important membrane glycoproteins for development and maturation of the retina. The gene encodes two immunoglobulin-like, membrane-bound glycoproteins as a result of splice variation. The smaller protein product, named 5A11/Basigin, is expressed by many tissues within the mouse, whereas the larger protein product, named 5A11/Basigin-2, is expressed only by the photoreceptor cells (PCs) of the retina. Mice in which the gene for 5A11/Basigin has been deleted have several abnormalities, including blindness from the time of eye opening with subsequent degeneration of the PCs. Studies by this laboratory suggest that a developmental deficiency is the underlying cause of the blindness. However, definitive biological functions for 5A11/Basigin and 5A11/Basigin-2 have yet to be defined. It is known that 5A11/Basigin is multifunctional and can interact with several different proteins. Preliminary studies indicate that 5A11/Basigin-2 may be multifunctional as well. Studies by this laboratory and others have demonstrated that 5A11/Basigin (and probably 5A11/Basigin-2) acts as a chaperone for monocarboxylate transporter-1 (MCT-1) translocation to the cell membrane. We have proposed that a lactate metabolon exists within the retina and functions to shuttle lactate, an energy source, from glial cells to the PCs. This metabolon is not present within 5A11/Basigin null mouse retinas, which may be the underlying cause of the retinal dysfunction and subsequent degeneration. Further studies will be necessary to determine which of the functions are critical for proper development of the retina.

Probing Metabolism in the Intact Retina Using Stable Isotope Tracers

“…Removal of glucose, inhibition of glycolysis, or deprivation of oxygen rapidly diminishes the ability of the retina to respond to light (Ames et al, 1992; Kang Derwent & Linsenmeier, 2000). Deficiencies of key enzymes and transporters in glucose metabolism cause retinal degeneration (Bui, Kalloniatis, & Vingrys, 2004; Maurer, Schonthaler, Mueller, & Neuhauss, 2010; Ochrietor & Linser, 2004). Neurons in the retina require metabolic support from glial cells.…”

The Neuroplastins: Multifunctional Neuronal Adhesion Molecules—Involvement in Behaviour and Disease

“…The critical importance of lactate transport for some tissues is well illustrated in homozygous basigin knockout mice. These mice are blind from the time of eye-opening with subsequent degeneration of the photoreceptors (Hori et al 2000 ;Philp et al 2003 ;Ochrietor and Linser 2004 ). This is most likely caused by the observed failure of MCT1 and MCT4 to integrate into the plasma membranes of the Muller glial cells and photoreceptors, although the level of MCT1 transcript is unaffected.…”

Characterization of Monocarboxylate Transporter 1 (MCT1) Binding Affinity for Basigin Gene Products and L1cam

“…There are two Basigin gene products in the retina, named Basigin and Basigin-2 . Basigin is expressed by epithelial cells throughout the body, as well as Müller cells, RPE and blood vessel endothelial cells of the mammalian retina (reviewed in Ochrietor and Linser 2004). Conversely, Basigin-2 is expressed only in the retina by photoreceptor cells .…”

“…The proposed shuttle is hypothesized to transport lactate from Müller cells to the photoreceptor cells to fuel oxidative phosphorylation (Philip et al 2003). It has been proposed that blindness observed in Basigin null mice is attributed to deficient photoreceptor metabolism due to the absence of the lactate shuttle (Ochrietor and Linser 2004).…”