Seminolipid and its precursor/degradative product, galactosylalkylacylglycerol, in the testis of saposin A- and prosaposin-deficient mice

Keiko Tadano-Aritomi,Junko Matsuda,Hirokazu Fujimoto,Kunihiko Suzuki,Ineo Ishizuka

doi:10.1194/jlr.m300119-jlr200

Abstract

Sphingolipid activator proteins (saposins A, B, C, and D) are derived from a common precursor protein (prosaposin) and specifically activate in vivo degradation of glycolipids with short carbohydrate chains. A mouse model of prosaposin deficiency (prosaposin-/-) closely mimics the human disease with an elevation of multiple glycolipids. The recently developed saposin A-/- mice showed a chronic form of globoid cell leukodystrophy, establishing the essential in vivo role of saposin A as an activator for galactosylceramidase to degrade galactosylceramide. Seminolipid, the principal glycolipid in spermatozoa, and its precursor/degradative product, galactosylalkylacylglycerol (GalEAG), were analyzed in the testis of the two mouse mutants by electrospray ionization mass spectrometry. Saposin A-/- mice showed the normal seminolipid level, while that of prosaposin-/- mice was approximately 150% of the normal level at the terminal stage. In contrast, GalEAG increased up to 10 times in saposin A-/- mice, whereas it decreased with age in the wild-type as well as in prosaposin-/- mice. These analytical findings on the two saposin mutants may shed some light on the physiological function of seminolipid and GalEAG.

Highlights

IntroductionSphingolipid activator proteins (saposins A, B, C, and D) are derived from a common precursor protein (prosaposin) and activate in vivo degradation of glycolipids with short carbohydrate chains
Sphingolipid activator proteins are derived from a common precursor protein and activate in vivo degradation of glycolipids with short carbohydrate chains
GalEAG is synthesized by galactosylation of alkylacylglycerol (EAG) by UDP-galactose:ceramide galactosyltransferase (CGT, EC 2.4.1.62) and is likely to be degraded by galactosylceramidase, which is deficient in globoid cell leukodystrophy

Summary

Introduction

Sphingolipid activator proteins (saposins A, B, C, and D) are derived from a common precursor protein (prosaposin) and activate in vivo degradation of glycolipids with short carbohydrate chains. Seminolipid, the principal glycolipid in spermatozoa, and its precursor/degradative product, galactosylalkylacylglycerol (GalEAG), were analyzed in the testis of the two mouse mutants by electrospray ionization mass spectrometry. Human patients with mutations in the saposin B and C domains show phenotypes of metachromatic leukodystrophy and Gaucher disease, indicating that saposins B and C are essential for in vivo degradation of galactosylsulfatide [galactosylceramide (GalCer) I3-sulfate] and glucosylceramide by arylsulfatase A and galactosylceramidase, respectively [2, 3]. We have analyzed seminolipid and GalEAG in the testis of the two mouse models, saposin AϪ/Ϫ and prosaposinϪ/Ϫ with a sensitive analytical method using mass spectrometry in order to investigate the effect of the saposin/prosaposin abnormalities on glycolipid metabolism and function of the testis

Methods

Results

Conclusion