Disease relevance of Scarb2

• Serious hearing impairment in LIMP-2-deficient animals was indicated by deficits in acoustic startle responses, in brainstem evoked auditory potentials and a reduced endochondral potential [1].
• LIMP-2-deficient mice show an increased postnatal mortality which is associated with a development of a uni- or bilateral hydronephrosis caused by an obstruction of the ureteropelvic junction [1].
• Here we show that LIMP2-deficient mice display a progressive high-frequency hearing loss and decreased otoacoustic emissions as early as 4 weeks of age [2].

High impact information on Scarb2

• The phenotype of LIMP-2-deficient mice stimulates the search for mutations in human disorders associated with degeneration of the stria vascularis and/or demyelinization of peripheral nerves [1].
• LIMP-2-deficient mice suffer from a massive decline of spiral ganglia in the cochlea concomitant with that of the inner and outer hair cells [1].
• Although LIMP2 is normally expressed in all cells of the stria vascularis, in the organ of Corti and cochlear neurons, the lack of LIMP2 preferentially caused a loss of KCNQ1/KCNE1 and megalin, and structural changes were only seen months later, indicating that these proteins are highly sensitive to disturbances in the lysosomal pathway [2].
• We previously have purified and characterized a major lysosomal membrane glycoprotein termed LGP85 (LIMP II) in rat liver lysosomes [3].
• In this study, LGP85 in mouse liver lysosomes was identified and characterized by biochemical and molecular biological methods [3].

Biological context of Scarb2

• A cDNA encoding M-LGP85 was cloned from mouse liver cDNA library [3].
• The primary protein structure deduced from a nucleotide sequence of M-LGP85 cDNA indicated that M-LGP85 consists of 478 amino acids with Mr of 54,069 [3].

Anatomical context of Scarb2

• Mouse LGP85 (M-LGP85) from liver lysosomal membranes exhibited an Mr of 80,000 on SDS-PAGE, which is smaller by 5,000 than that of rat LGP85 (R-LGP85) [3].
• Deafness in LIMP2-deficient mice due to early loss of the potassium channel KCNQ1/KCNE1 in marginal cells of the stria vascularis [2].

Associations of Scarb2 with chemical compounds

• It is likely that M-LGP85 traverses the lysosomal membrane twice, with an NH2-terminal transmembrane domain, and another hydrophobic domain near the COOH-terminus [3].

Other interactions of Scarb2

• Our findings suggest an important role for LIMP2 in the control of the localization and the level of apically expressed membrane proteins such as KCNQ1, KCNE1 and megalin in the stria vascularis [2].

Analytical, diagnostic and therapeutic context of Scarb2

• Immunofluorescence analysis revealed that TRP-1, a melanosomal membrane protein, did not colocalize with lysosomal membrane proteins LAMP1 and LGP85 in melan-a cells [4].

References