Aims: 

Acetylcholinesterase (AChE), the key the enzyme for the degradation of acetylcholine, is associated to the plasma membrane in the brain but also secreted in the extracellular space. The objective of this study was to evaluate the importance of the membrane anchor, PRiMA, in the localization of AChE.

Methods: 

We generated a single PRiMA mutant by an insertion in the exon encoding the domain interaging with AChE. In addition double mutant was generated, in which, we used an allele of AChE in which the last exon encoding the domain interacting with PRiMA is deleted. In the striatum of simple or double mutants, we localized AChE with specific antibodies at light and electron microscopy.

Results: 

In normal mouse, AChE is highly accumulated at the surface of the axon and of cell body and also in the secretory pathway. In PRiMA mutant, AChE is completely absent from the axon as expected. Surprisingly, AChE is only accumulated in the endoplasmic reticulum and completely absent in the Golgi apparatus and cell surface. In contrast, in the double mutant PRiMA/allele AChE, AChE is found both in the ER and the Golgi apparatus but absent from the cell surface.

Conclusion: 

These results show that PRiMA is essential for AChE and has two functions: (1) targeting AChE to the axon and the cell surface and (2) maturation of AChE through the secretory pathway.