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

@article{citeulike:4191627, 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.}, author = {Linhoff, M. W. and Laur\'{e}n, J. and Cassidy, R. M. and Dobie, F. A. and Takahashi, H. and Nygaard, H. B. and Airaksinen, M. S. and Strittmatter, S. M. and Craig, A. M.}, citeulike-article-id = {4191627}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.neuron.2009.01.017}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19285470}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19285470}, day = {12}, doi = {10.1016/j.neuron.2009.01.017}, issn = {1097-4199}, journal = {Neuron}, month = {March}, number = {5}, pages = {734--749}, posted-at = {2009-03-18 09:47:33}, priority = {2}, title = {An unbiased expression screen for synaptogenic proteins identifies the LRRTM protein family as synaptic organizers.}, url = {http://dx.doi.org/10.1016/j.neuron.2009.01.017}, volume = {61}, year = {2009} }

TY - JOUR ID - citeulike:4191627 L3 - citeulike-article-id:4191627 N2 - 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. IS - 5 JF - Neuron SN - 1097-4199 EP - 749 TI - An unbiased expression screen for synaptogenic proteins identifies the LRRTM protein family as synaptic organizers. VL - 61 SP - 734 AU - Linhoff, MW AU - Laurén, J AU - Cassidy, RM AU - Dobie, FA AU - Takahashi, H AU - Nygaard, HB AU - Airaksinen, MS AU - Strittmatter, SM AU - Craig, AM PY - 2009/03/12/ UR - http://dx.doi.org/10.1016/j.neuron.2009.01.017 ER -