Sphingolipids and lysosomal pathologies

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• 作者：Heike Schulze ; Konrad Sandhoff ; ^{sandhoff@uni-bonn.de" class="auth_mail}
• 关键词：ASM ; acid sphingomyelinase ; BMP ; bis(monoacylglycero)phosphate ; Cer ; ceramide ; ER ; endoplasmic reticulum ; ERT ; enzyme replacement therapy ; ESCRT ; endosomal sorting complex required for transport ; FA ; fatty acid ; GalCer ; galactosylceramide ; GlcCer ; glucosylceramide ; GM2-AP ; GM2 activator protein ; GSL ; glycosphingolipid ; IM ; inner membranes ; HSAN1 ; hereditary sensory neuropathy type I ; LacCer ; lactosylceramide ; LIMP-2 ; lysosomal integral membrane protein type 2 ; NPC-1 ; Niemann&ndash ; Pick C1 protei
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids
• 出版年：May, 2014
• 年：2014
• 卷：1841
• 期：5
• 页码：799-810
• 全文大小：1824 K

文摘

Endocytosed (glyco)sphingolipids are degraded, together with other membrane lipids in a stepwise fashion by endolysosomal enzymes with the help of small lipid binding proteins, the sphingolipid activator proteins (SAPs), at the surface of intraluminal lysosomal vesicles. Inherited defects in a sphingolipid-degrading enzyme or SAP cause the accumulation of the corresponding lipid substrates, including cytotoxic lysosphingolipids, such as galactosylsphingosine and glucosylsphingosine, and lead to a sphingolipidosis. Analysis of patients with prosaposin deficiency revealed the accumulation of intra-endolysosmal vesicles and membrane structures (IM). Feeding of prosaposin reverses the storage, suggesting inner membrane structures as platforms of sphingolipid degradation. Water soluble enzymes can hardly attack sphingolipids embedded in the membrane of inner endolysosomal vesicles. The degradation of sphingolipids with few sugar residues therefore requires the help of the SAPs, and is strongly stimulated by anionic membrane lipids. IMs are rich in anionic bis(monoacylglycero)phosphate (BMP). This article is part of a Special Issue entitled New Frontiers in Sphingolipid Biology.