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Reep1 null mice reveal a converging role for hereditary spastic paraplegia proteins in lipid droplet regulation.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Renvoisé, Benoît Malone, Brianna Falgairolle, Mélanie Munasinghe, Jeeva Prasanna Stadler, Julia Sibilla, Caroline Park, Seong Hoon Blackstone, Craig |
| Copyright Year | 2016 |
| Abstract | Hereditary spastic paraplegias (HSPs; SPG1-76 plus others) are length-dependent disorders affecting long corticospinal axons, and the most common autosomal dominant forms are caused by mutations in genes that encode the spastin (SPG4), atlastin-1 (SPG3A) and REEP1 (SPG31) proteins. These proteins bind one another and shape the tubular endoplasmic reticulum (ER) network throughout cells. They also are involved in lipid droplet formation, enlargement, or both in cells, though mechanisms remain unclear. Here we have identified evidence of partial lipoatrophy in Reep1 null mice in addition to prominent spastic paraparesis. Furthermore, Reep1-/- embryonic fibroblasts and neurons in the cerebral cortex both show lipid droplet abnormalities. The apparent partial lipodystrophy in Reep1 null mice, although less severe, is reminiscent of the lipoatrophy phenotype observed in the most common form of autosomal recessive lipodystrophy, Berardinelli-Seip congenital lipodystrophy. Berardinelli-Seip lipodystrophy is caused by autosomal recessive mutations in the BSCL2 gene that encodes an ER protein, seipin, that is also mutated in the autosomal dominant HSP SPG17 (Silver syndrome). Furthermore, REEP1 co-immunoprecipitates with seipin in cells. This strengthens the link between alterations in ER morphogenesis and lipid abnormalities, with important pathogenic implications for the most common forms of HSP. |
| Starting Page | 5111 |
| Ending Page | 5125 |
| Page Count | 15 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://ezbiosystems.com/pdf/publ/Renvoise_B.pdf |
| PubMed reference number | 27638887v1 |
| Alternate Webpage(s) | https://doi.org/10.1093/hmg/ddw315 |
| DOI | 10.1093/hmg/ddw315 |
| Journal | Human molecular genetics |
| Volume Number | 25 |
| Issue Number | 23 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | ATL1 gene Autosomal dominant inheritance Autosomal recessive inheritance Axon BSCL2 gene Cerebral cortex Congenital Abnormality Convergence (action) Encode (action) Endoplasmic Reticulum Familial generalized lipodystrophy Heat Shock Protein HSP 90-Beta Henoch-Schoenlein Purpura Hyper-Immunoglobulin E Syndrome, Autosomal Recessive Hypertrophy Lipid Metabolism Disorders Lipoatrophy MASA SYNDROME (disorder) Morphogenesis Muscle Spasticity Mutation Null Value Paraparesis Paraparesis, Spastic Paraplegia REEP1 gene SPAST gene Spastic Paraplegia, Hereditary |
| Content Type | Text |
| Resource Type | Article |
