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

• Published in: Biochimica et biophysica acta Vol. 1802; no. 9; pp. 754 - 764
• Main Authors: Moral-Naranjo, María Teresa, Montenegro, María Fernanda, Muñoz-Delgado, Encarnación, Campoy, Francisco J., Vidal, Cecilio J.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-09-2010; Elsevier
• Subjects: 5'-Nucleotidase - metabolism; 5'-Nucleotidase - physiology; Acetylcholinesterase - genetics; Acetylcholinesterase - metabolism; Acetylcholinesterase - physiology; Animals; Caveolae; Caveolin 3 - genetics; Caveolin 3 - metabolism; Cholinesterase; Ecto-5’-nucleotidase (CD73); Laminin - deficiency; Laminin - genetics; Membrane Microdomains - metabolism; Membrane Microdomains - pathology; Mice; Mice, Inbred C57BL; Mice, Transgenic; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Muscular dystrophy; Muscular Dystrophy, Animal - metabolism; Muscular Dystrophy, Animal - pathology; Protein Multimerization; Ecto-5’-nucleotidase (CD73); Caveolae; Cholinesterase; Muscular dystrophy; ecto-5′-nucleotidase (CD73); Cholinesterases
• ISSN: 0925-4439; 0006-3002; 1879-260X
• DOI: 10.1016/j.bbadis.2010.05.011

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.