Retrograde regulation of mossy fiber axon targeting and terminal maturation via postsynaptic Lnx1

Xian Dong Liu, Xiao Na Zhu, Michael M. Halford, Tian Le Xu, Mark J Henkemeyer, Nan Jie Xu

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Neuronal connections are initiated by axon targeting to form synapses. However, how the maturation of axon terminals is modulated through interacting with postsynaptic elements remains elusive. In this study, we find that ligand of Numb protein X 1 (Lnx1), a postsynaptic PDZ protein expressed in hippocampal CA3 pyramidal neurons, is essential for mossy fiber (MF) axon targeting during the postnatal period. Lnx1 deletion causes defective synaptic arrangement that leads to aberrant presynaptic terminals. We further identify EphB receptors as novel Lnx1-binding proteins to form a multiprotein complex that is stabilized on the CA3 neuron membrane through preventing proteasome activity. EphB1 and EphB2 are independently required to transduce distinct signals controlling MF pruning and targeting for precise DG-CA3 synapse formation. Furthermore, constitutively active EphB2 kinase rescues structure of the wired MF terminals in Lnx1 mutant mice. Our data thus define a retrograde trans-synaptic regulation required for integration of post- and presynaptic structure that participates in building hippocampal neural circuits during the adolescence period.

Original languageEnglish (US)
Pages (from-to)4007-4024
Number of pages18
JournalJournal of Cell Biology
Issue number11
StatePublished - Nov 1 2018

ASJC Scopus subject areas

  • Cell Biology


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