The levels of both lipid rafts and raft-located acetylcholinesterase dimers increase in muscle of mice with muscular dystrophy by merosin deficiency

María Teresa Moral-Naranjo (1) , María Fernanda Montenegro (1) , Encarnación Muñoz-Delgado (1) , Francisco J. Campoy (1) , Cecilio J. Vidal (1)

1 Departamento de Bioquímica y Biología Molecular-A

Wild type and dystrophic (merosin-deficient) 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) dimmers, 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 muscle provided for a rational explanation to the loss of PRiMA-bearing AChE tetramers in dystrophic muscle.

Mots clés: Caveolae; Cholinesterases; ecto-5′-nucleotidase (CD73); Muscular dystrophy

María Teresa Moral-Naranjo, María Fernanda Montenegro, Encarnación Muñoz-Delgado, Francisco J. Campoy, Cecilio J. Vidal. The levels of both lipid rafts and raft-located acetylcholinesterase dimers increase in muscle of mice with muscular dystrophy by merosin deficiency. Biochimica et Biophysica Acta - Molecular Basis of Disease, 2010, 1802 (9), pp.754. ⟨10.1016/j.bbadis.2010.05.011⟩. ⟨hal-00608980⟩