Postsynaptic TrkC and Presynaptic PTP sigma Function as a Bidirectional Excitatory Synaptic Organizing Complex

作者：Takahashi Hideto; Arstikaitis Pamela; Prasad Tuhina; Bartlett Thomas E; Wang Yu Tian; Murphy Timothy H; Craig Ann Marie^*

来源：Neuron, 2011, 69(2): 287-303.

DOI：10.1016/j.neuron.2010.12.024

Neurotrophin receptor tyrosine kinases (Trks) have well-defined trophic roles in nervous system development through kinase activation by neurotrophins. Yet Trks have typical cell-adhesion domains and express noncatalytic isoforms, suggesting additional functions. Here we discovered noncatalytic TrkC in an unbiased hippocampal neuron-fibroblast coculture screen for proteins that trigger differentiation of neurotransmitter release sites in axons. All TrkC isoforms, but not TrkA or TrkB, function directly in excitatory glutamatergic synaptic adhesion by neurotrophin-independent high-affinity trans binding to axonal protein tyrosine phosphatase receptor PTP sigma. PTP sigma triggers and TrkC mediates clustering of postsynaptic molecules in dendrites, indicating bidirectional synaptic organizing functions. Effects of a TrkC-neutralizing antibody that blocks TrkC-PTP sigma interaction and TrkC knockdown in culture and in vivo reveal essential roles of TrkC-PTP sigma in glutamatergic synapse formation. Thus, postsynaptic TrkC trans interaction with presynaptic PTP sigma generates bidirectional adhesion and recruitment essential for excitatory synapse development and positions these signaling molecules at the center of synaptic pathways.

• 出版日期2011-1-27