Abstract:
:Delineating the molecular basis of synapse development is crucial for understanding brain function. Cocultures of neurons with transfected fibroblasts have demonstrated the synapse-promoting activity of candidate molecules. Here, we performed an unbiased expression screen for synaptogenic proteins in the coculture assay using custom-made cDNA libraries. Reisolation of NGL-3/LRRC4B and neuroligin-2 accounts for a minority of positive clones, indicating that current understanding of mammalian synaptogenic proteins is incomplete. We identify LRRTM1 as a transmembrane protein that induces presynaptic differentiation in contacting axons. All four LRRTM family members exhibit synaptogenic activity, LRRTMs localize to excitatory synapses, and artificially induced clustering of LRRTMs mediates postsynaptic differentiation. We generate LRRTM1(-/-) mice and reveal altered distribution of the vesicular glutamate transporter VGLUT1, confirming an in vivo synaptic function. These results suggest a prevalence of LRR domain proteins in trans-synaptic signaling and provide a cellular basis for the reported linkage of LRRTM1 to handedness and schizophrenia.
journal_name
Neuronjournal_title
Neuronauthors
Linhoff MW,Laurén J,Cassidy RM,Dobie FA,Takahashi H,Nygaard HB,Airaksinen MS,Strittmatter SM,Craig AMdoi
10.1016/j.neuron.2009.01.017subject
Has Abstractpub_date
2009-03-12 00:00:00pages
734-49issue
5eissn
0896-6273issn
1097-4199pii
S0896-6273(09)00084-1journal_volume
61pub_type
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