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Analysis of adhesion molecules and basement membrane contributions to synaptic adhesion at the Drosophila embryonic NMJ

Koper, A., Schenck, A., Prokop, A

PloS One. 2012;7(4):e36339.

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Abstract

Synapse formation and maintenance crucially underlie brain function in health and disease. Both processes are believed to depend on cell adhesion molecules (CAMs). Many different classes of CAMs localise to synapses, including cadherins, protocadherins, neuroligins, neurexins, integrins, and immunoglobulin adhesion proteins, and further contributions come from the extracellular matrix and its receptors. Most of these factors have been scrutinised by loss-of-function analyses in animal models. However, which adhesion factors establish the essential physical links across synaptic clefts and allow the assembly of synaptic machineries at the contact site in vivo is still unclear. To investigate these key questions, we have used the neuromuscular junction (NMJ) of Drosophila embryos as a genetically amenable model synapse. Our ultrastructural analyses of NMJs lacking different classes of CAMs revealed that loss of all neurexins, all classical cadherins or all glutamate receptors, as well as combinations between these or with a Laminin deficiency, failed to reveal structural phenotypes. These results are compatible with a view that these CAMs have no structural role at this model synapse. However, we think it far more likely that they operate in redundant or well buffered context. We propose a model based on a multi-adaptor principle to explain this phenomenon. Furthermore, we report a new CAM-independent adhesion mechanism that involves the basement membranes (BM) that cover neuromuscular terminals. Thus, motorneuronal terminals show strong partial detachment of the junction when BM-to-cell surface attachment is impaired by removing Laminin A, or when BMs lose their structural integrity upon loss of type IV collagens. We conclude that BMs are essential to tie embryonic motorneuronal terminals to the muscle surface, lending CAM-independent structural support to their adhesion. Therefore, future developmental studies of these synaptic junctions in Drosophila need to consider the important contribution made by BM-dependent mechanisms, in addition to CAM-dependent adhesion. PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22558441

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7
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4
Pagination:
e36339
Digital Object Identifier:
10.1371/journal.pone.0036339
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Active

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Manchester eScholar ID:
uk-ac-man-scw:158385
Created by:
Prokop, Andreas
Created:
31st March, 2012, 04:50:52
Last modified by:
Prokop, Andreas
Last modified:
27th October, 2012, 17:14:26

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