Shaping the sperm head: an ER enzyme leaves its mark
Angshumoy Roy, … , Yi-Nan Lin, Martin M. Matzuk
Angshumoy Roy, … , Yi-Nan Lin, Martin M. Matzuk
Published November 1, 2006
Citation Information: J Clin Invest. 2006;116(11):2860-2863. https://doi.org/10.1172/JCI30221.
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Commentary

Shaping the sperm head: an ER enzyme leaves its mark

Abstract

Lipid storage diseases are debilitating inherited metabolic disorders that stem from the absence of specific lysosomal enzymes that degrade selected lipids. Most characteristically, these disorders affect the nervous and the reticulo-endothelial systems, with massive organomegaly resulting from the presence of engorged, lipid-laden macrophages. In this issue of the JCI, Yildiz et al. describe the role of the ER-resident enzyme β-glucosidase 2 (GBA2) in mice (see the related article beginning on page 2985). Surprisingly, GBA2 deficiency leaves bile acid and cholesterol metabolism intact, instead causing lipid accumulation in the ER of testicular Sertoli cells, round-headed sperm (globozoospermia), and impaired male fertility.

Authors

Angshumoy Roy, Yi-Nan Lin, Martin M. Matzuk

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Figure 1

Schematic showing subcellular localization and functions of enzymes involved in glucosylceramide metabolism.

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Schematic showing subcellular localization and functions of enzymes invo...
Top inset: GBA2 hydrolyzes the glucose moiety from glucosylceramides (GlcCer) at the neutral pH of the ER lumen. A nonlysosomal glucosylceramidase (likely GBA2) is inhibited by NB-DNJ. Middle inset: UDP-glucose ceramide glucosyltransferase (UGCG) on the Golgi surface synthesizes glucosylceramide and is inhibited by NB-DNJ. After synthesis, glucosylceramide is flipped back into the Golgi lumen. Bottom inset: Glucosylceramides phagocytosed into the cell are normally degraded in the acidic pH of the lysosome by GBA. The phenotypes of Gba- and Gba2-null mice are described at right.