This report describes work done with the fly gene spin, based on the observation that intracellular accumulation of lipids and enlarged dysfunctional lysosomes are linked to several neurodegenerative diseases. Dmel\spin encodes a conserved transmembrane lysosomal efflux transporter of sphingolipids and other lysosome cargoes. Classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for spin.
There are three orthologous genes in human, SPNS1, SPNS2, and SPNS3. The human genes have not been associated with human disease by OMIM, but there is evidence that SPNS2 may play roles in the progression of lung cancer and in progressive hearing loss. None of the orthologous human genes has been introduced into flies.
Animals homozygous for hypomorphic mutations of Dmel\spin exhibit decreased adult life span, defects in courtship behavior, accumulation of enlarged autolysosomes, and neurodegeneration. Physical and genetic interactions have been described for Dmel\spin; see below and in the gene report for spin.
[updated Apr. 2018 by FlyBase; FBrf0222196]
Lysosomal storage diseases are inherited metabolic diseases that are characterized by an abnormal build-up of various toxic materials in the body's cells as a result of enzyme deficiencies. [NORD, Lysosomal Storage Disorders; 2018.04.16]
Lysosomal storage diseases describe a heterogeneous group of dozens of rare inherited disorders characterized by the accumulation of undigested or partially digested macromolecules, which ultimately results in cellular dysfunction and clinical abnormalities (https://emedicine.medscape.com/article/1182830-overview).
Most lysosomal storage disorders are inherited in an autosomal recessive manner. [NORD, Lysosomal Storage Disorders; 2018.04.16]
Lysosomal storage diseases (LSDs) result in accumulation of undegraded products in lysosomes. This causes enlargement of cells (ballooning), cellular dysfunction, and cell death. On electron microscopic examination, the stored products are membrane-bound because they are contained within lysosomes (http://neuropathology-web.org/chapter10/chapter10aLSDgeneral.html).
Sphingolipids consist of a backbone of ceramide with attached oligosaccharide side chains. They are major constituents of cell membranes (http://neuropathology-web.org/chapter10/chapter10aLSDgeneral.html).
SPNS2 (sphingolipid transporter 2) encodes a transporter of sphingosine 1-phosphate, a secreted lipid that is important in cardiovascular, immunological, and neural development. [Gene Cards, SPNS2; 2018.04.16]
Many to one: 3 human to 1 Drosophila. The human genes are SPNS1, SPNS2, and SPNS3; there is an additional low-scoring ortholog in fly.
Many to one: 3 human to 1 Drosophila. The human genes are SPNS1, SPNS2, and SPNS3; there is an additional low-scoring ortholog in fly.
Many to one: 3 human to 1 Drosophila. The human genes are SPNS1, SPNS2, and SPNS3; there is an additional low-scoring ortholog in fly.
High-scoring ortholog of human SPNS1, SPNS2, and SPNS3 (1 Drosophila to 3 human); there is an additional low-scoring ortholog in fly. Dmel\spin shares 38-48% identity and 52-61% similarity with the human genes.
