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PLoS One. 2014 Feb 27;9(2):e89763. doi: 10.1371/journal.pone.0089763. eCollection 2014.

Afadin regulates puncta adherentia junction formation and presynaptic differentiation in hippocampal neurons.

Author information

1
Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan ; CREST, Japan Science and Technology Agency, Kobe, Hyogo, Japan.
2
Faculty of Health Sciences, Kobe University Graduate School of Health Sciences, Kobe, Hyogo, Japan ; CREST, Japan Science and Technology Agency, Kobe, Hyogo, Japan.

Abstract

The formation and remodeling of mossy fiber-CA3 pyramidal cell synapses in the stratum lucidum of the hippocampus are implicated in the cellular basis of learning and memory. Afadin and its binding cell adhesion molecules, nectin-1 and nectin-3, together with N-cadherin, are concentrated at puncta adherentia junctions (PAJs) in these synapses. Here, we investigated the roles of afadin in PAJ formation and presynaptic differentiation in mossy fiber-CA3 pyramidal cell synapses. At these synapses in the mice in which the afadin gene was conditionally inactivated before synaptogenesis by using nestin-Cre mice, the immunofluorescence signals for the PAJ components, nectin-1, nectin-3 and N-cadherin, disappeared almost completely, while those for the presynaptic components, VGLUT1 and bassoon, were markedly decreased. In addition, these signals were significantly decreased in cultured afadin-deficient hippocampal neurons. Furthermore, the interevent interval of miniature excitatory postsynaptic currents was prolonged in the cultured afadin-deficient hippocampal neurons compared with control neurons, indicating that presynaptic functions were suppressed or a number of synapse was reduced in the afadin-deficient neurons. Analyses of presynaptic vesicle recycling and paired recordings revealed that the cultured afadin-deficient neurons showed impaired presynaptic functions. These results indicate that afadin regulates both PAJ formation and presynaptic differentiation in most mossy fiber-CA3 pyramidal cell synapses, while in a considerable population of these neurons, afadin regulates only PAJ formation but not presynaptic differentiation.

PMID:
24587018
PMCID:
PMC3937348
DOI:
10.1371/journal.pone.0089763
[Indexed for MEDLINE]
Free PMC Article

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