Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dystrophin forms an essential link between sarcolemma and cytoskeleton, perturbation of which causes muscular dystrophy. We analysed Dystrophin binding dynamics in vivo for the first time. Within maturing fibres of host zebrafish embryos, our analysis reveals a pool of diffusible Dystrophin and complexes bound at the fibre membrane. Combining modelling, an improved FRAP methodology and direct semi-quantitative analysis of bleaching suggests the existence of two membrane-bound Dystrophin populations with widely differing bound lifetimes: a stable, tightly bound pool, and a dynamic bound pool with high turnover rate that exchanges with the cytoplasmic pool. The three populations were found consistently in human and zebrafish Dystrophins overexpressed in wild-type or dmd(ta222a/ta222a) zebrafish embryos, which lack Dystrophin, and in Gt(dmd-Citrine)(ct90a) that express endogenously-driven tagged zebrafish Dystrophin. These results lead to a new model for Dystrophin membrane association in developing muscle, and highlight our methodology as a valuable strategy for in vivo analysis of complex protein dynamics.
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PMID:In vivo dynamics of skeletal muscle Dystrophin in zebrafish embryos revealed by improved FRAP analysis. 2645 31

Golgi apparatus (GA) is a membrane-bound organelle that serves a multitude of critical cellular functions including protein secretion and sorting, and cellular polarity. Many Mendelian diseases are caused by mutations in genes encoding various components of GA. GOLGA2 encodes GM130, a necessary component for the assembly of GA as a single complex, and its deficiency has been found to result in severe cellular phenotypes. We describe the first human patient with a homozygous apparently loss of function mutation in GOLGA2. The phenotype is a neuromuscular disorder characterized by developmental delay, seizures, progressive microcephaly, and muscular dystrophy. Knockdown of golga2 in zebrafish resulted in severe skeletal muscle disorganization and microcephaly recapitulating loss of function human phenotype. Our data suggest an important developmental role of GM130 in humans and zebrafish.
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PMID:GOLGA2, encoding a master regulator of golgi apparatus, is mutated in a patient with a neuromuscular disorder. 2674 1

The Popeye domain containing (POPDC) gene family encodes a novel class of membrane-bound cyclic AMP effector proteins. POPDC proteins are abundantly expressed in cardiac and skeletal muscle. Consistent with its predominant expression in striated muscle, Popdc1 and Popdc2 null mutants in mouse and zebrafish develop cardiac arrhythmia and muscular dystrophy. Likewise, mutations in POPDC genes in patients have been associated with cardiac arrhythmia and muscular dystrophy phenotypes. A membrane trafficking function has been identified in this context. POPDC proteins have also been linked to tumour formation. Here, POPDC1 plays a role as a tumour suppressor by limiting c-Myc and WNT signalling. Currently, a common functional link between POPDC's role in striated muscle and as a tumour suppressor is lacking. We also discuss several alternative working models to better understand POPDC protein function.
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PMID:The Popeye domain containing gene family encoding a family of cAMP-effector proteins with important functions in striated muscle and beyond. 3119 1


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