Leucine-rich repeat transmembrane proteins are essential for maintenance of long-term potentiation.
Leucine-rich repeat transmembrane proteins (LRRTMs) are synaptic cell adhesion molecules that trigger excitatory synapse assembly in cultured neurons and influence synaptic function in vivo, but their role in synaptic plasticity is unknown. shRNA-mediated knockdown (KD) of LRRTM1 and LRRTM2 in vivo in CA1 pyramidal neurons of newborn mice blocked long-term potentiation (LTP) in acute hippocampal slices. Molecular replacement experiments revealed that the LRRTM2 extracellular domain is sufficient for LTP, probably because it mediates binding to neurexins (Nrxs). Examination of surface expression of endogenous AMPA receptors (AMPARs) in cultured neurons suggests that LRRTMs maintain newly delivered AMPARs at synapses after LTP induction. LRRTMs are also required for LTP of mature synapses on adult CA1 pyramidal neurons, indicating that the block of LTP in neonatal synapses by LRRTM1 and LRRTM2 KD is not due to impairment of synapse maturation.
Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA 94305, USA.
Gilberto J
GJ
Soler-Llavina
Pamela
P
Arstikaitis
Wade
W
Morishita
Mohiuddin
M
Ahmad
Thomas C
TC
Südhof
Robert C
RC
Malenka
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects / Q000235:genetics; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D006801:Humans; D017774:Long-Term Potentiation / Q000502:physiology*; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D034741:RNA, Small Interfering / Q000378:metabolism; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000502:physiology*; D013997:Time Factors; D014161:Transduction, Genetic; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D034741:RNA, Small Interfering; D018091:Receptors, AMPA; D050598:Vesicular Glutamate Transport Protein 1; C561490:LRRTM1 protein, mouse; C561491:LRRTM2 protein, mouse