Title : A secreted complement-control-related protein ensures acetylcholine receptor clustering - Gendrel_2009_Nature_461_992
Author(s) : Gendrel M , Rapti G , Richmond JE , Bessereau JL
Ref : Nature , 461 :992 , 2009
Abstract :

Efficient neurotransmission at chemical synapses relies on spatial congruence between the presynaptic active zone, where synaptic vesicles fuse, and the postsynaptic differentiation, where neurotransmitter receptors concentrate. Diverse molecular systems have evolved to localize receptors at synapses, but in most cases, they rely on scaffolding proteins localized below the plasma membrane. A few systems have been suggested to control the synaptic localization of neurotransmitter receptors through extracellular interactions, such as the pentraxins that bind AMPA receptors and trigger their aggregation. However, it is not yet clear whether these systems have a central role in the organization of postsynaptic domains in vivo or rather provide modulatory functions. Here we describe an extracellular scaffold that is necessary to cluster acetylcholine receptors at neuromuscular junctions in the nematode Caenorhabditis elegans. It involves the ectodomain of the previously identified transmembrane protein LEV-10 (ref. 6) and a novel extracellular protein, LEV-9. LEV-9 is secreted by the muscle cells and localizes at cholinergic neuromuscular junctions. Acetylcholine receptors, LEV-9 and LEV-10 are interdependent for proper synaptic localization and physically interact based on biochemical evidence. Notably, the function of LEV-9 relies on eight complement control protein (CCP) domains. These domains, also called 'sushi domains', are usually found in proteins regulating complement activity in the vertebrate immune system. Because the complement system does not exist in protostomes, our results suggest that some of the numerous uncharacterized CCP proteins expressed in the mammalian brain might be directly involved in the organization of the synapse, independently from immune functions.

PubMedSearch : Gendrel_2009_Nature_461_992
PubMedID: 19794415

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Citations formats

Gendrel M, Rapti G, Richmond JE, Bessereau JL (2009)
A secreted complement-control-related protein ensures acetylcholine receptor clustering
Nature 461 :992

Gendrel M, Rapti G, Richmond JE, Bessereau JL (2009)
Nature 461 :992