RGD Reference Report - An unbiased expression screen for synaptogenic proteins identifies the LRRTM protein family as synaptic organizers. - Rat Genome Database

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An unbiased expression screen for synaptogenic proteins identifies the LRRTM protein family as synaptic organizers.

Authors: Linhoff, MW  Lauren, J  Cassidy, RM  Dobie, FA  Takahashi, H  Nygaard, HB  Airaksinen, MS  Strittmatter, SM  Craig, AM 
Citation: Linhoff MW, etal., Neuron. 2009 Mar 12;61(5):734-49. doi: 10.1016/j.neuron.2009.01.017.
RGD ID: 8554788
Pubmed: (View Article at PubMed) PMID:19285470
DOI: Full-text: DOI:10.1016/j.neuron.2009.01.017

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.

Annotation

Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
LRRTM1  (leucine rich repeat transmembrane neuronal 1)
Lrrtm2  (leucine rich repeat transmembrane neuronal 2)

Objects referenced in this article
0 Lrrtm4 leucine rich repeat transmembrane neuronal 4 All species
0 Nlgn2 neuroligin 2 All species

Additional Information