The levels of both lipid rafts and raft-located acetylcholinesterase dimers increase in muscle of mice with muscular dystrophy by merosin deficiency.
Wild type and dystrophic (merosin-deficient) Lama2dy mice muscles were compared for their density of lipid rafts. The 5-fold higher level of caveolin-3 and the 2-3 times higher level of ecto-5'-nucleotidase activity in raft preparations (Triton X-100-resistant membranes) of dystrophic muscle supported expansion of caveolar and non-caveolar lipid rafts. The presence in rafts of glycosylphosphatidylinositol (GPI)-linked acetylcholinesterase (AChE) dimers, which did not arise from erythrocyte or nerve, not only revealed for the first time the capacity of the myofibre for translating the AChE-H mRNA but also an unrecognized pathway for targeting AChE-H to specialized membrane domains of the sarcolemma. Rafts of dystrophic muscle contained a 5-fold higher AChE activity/mg protein. RT-PCR for 3'-alternative mRNAs of AChE revealed AChE-T mRNA prevailing over AChE-R and AChE-H mRNAs in wild type mouse muscle. It also displayed principal 5'-alternative AChE mRNAs with exons E1c and E1e (the latter coding for N-terminally extended subunits) and fewer with E1d, E1a and E1b. The levels of AChE and butyrylcholinesterase mRNAs were unaffected by dystrophy. Finally, the decreased level of proline-rich membrane anchor (PRiMA) mRNA in Lama2dy muscle provided for a rational explanation to the loss of PRiMA-bearing AChE tetramers in dystrophic muscle.
Moral-Naranjo
María Teresa
MT
Departamento de Bioquímica y Biología Molecular-A, Universidad de Murcia, Murcia, Spain.
Montenegro
María Fernanda
MF
Muñoz-Delgado
Encarnación
E
Campoy
Francisco J
FJ
Vidal
Cecilio J
CJ
D015720:5'-Nucleotidase / Q000378:metabolism / Q000502:physiology; D000110:Acetylcholinesterase / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D051244:Caveolin 3 / Q000235:genetics / Q000378:metabolism; D007797:Laminin / Q000172:deficiency / Q000235:genetics*; D021962:Membrane Microdomains / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009137:Muscular Dystrophy, Animal / Q000378:metabolism / Q000473:pathology*; D055503:Protein Multimerization
D051244:Caveolin 3; D007797:Laminin; D000110:Acetylcholinesterase; D015720:5'-Nucleotidase