Abstract
Abstract
Prosaposin, and its cleaved byproducts saposin A-D, are crucial proteins necessary for glycoshpingolipid degradation and metabolism. Mutations in these proteins can lead to devastating lysosomal storage diseases, including Gaucher’s disease, symptoms of which often include hearing loss. Until recently, little was known about the role that prosaposin and saposins A-D played in auditory and vestibular system function. Early studies in knockout mouse models showed prosaposin to be important for normal cochlear innervation and maintenance of normal hearing (Akil et al., 2006). Severe vestibular dysfunction paired with inclusion body accumulation in the vestibular end-organs of prosaposin KO mice suggests its role in the maintenance of normal hearing and the maturation of normal vestibular system function (Akil et al., 2012). To determine if these phenotypes were attributable to the loss of prosaposin as a whole or one of its constituent proteins, saposin A-D, KO mice of individual saposins were subsequently studied. Given the nature of the hearing loss, as well as efferent and afferent neuronal sprouting in the prosaposin KO mouse, it was hypothesized that saposin C, a protein known for its neurotigenic properties, was responsible for these changes. However, a null-mutant mouse lacking both saposin C and D showed no effect on hearing (Lustig et al., 2015). In contrast, a loss of functional saposin B led to a progressive sulfatide accumulation in satellite cells around cochlear spiral ganglion (SG) neurons resulting in satellite cell degeneration, SG degeneration, and ultimately, loss of hearing (Akil et al., 2015). While saposin B KO mice did not show any vestibular dysfunction phenotype, vestibular evoked potentials demonstrated profound vestibular dysfunction likely attributable to the large-scale neuronal degeneration (Akil et al., 2015). Furthermore, the data suggests that saposin B appears to have a much greater role in auditory neuronal maintenance and balance than saposin C and/or D.