A Preformed Complex of Postsynaptic Proteins Is Involved in Excitatory Synapse Development
نویسندگان
چکیده
Nonsynaptic clusters of postsynaptic proteins have been documented; however, their role remains elusive. We monitored the trafficking of several candidate proteins implicated in synaptogenesis, when nonsynaptic clusters of scaffold proteins are most abundant. We find a protein complex consisting of two populations that differ in their content, mobility, and involvement in synapse formation. One subpopulation is mobile and relies on actin transport for delivery to nascent and existing synapses. These mobile clusters contain the scaffolding proteins PSD-95, GKAP, and Shank. A proportion of mobile clusters that exhibits slow movement and travels short distances contains neuroligin-1. The second group consists of stationary nonsynaptic scaffold complexes that mainly contain neuroligin-1, can recruit synaptophysin-containing axonal transport vesicles, and are readily transformed to functional presynaptic contacts that recycle the vital dye FM 4-64. These results postulate a mechanism whereby preformed scaffold protein complexes serve as predetermined postsynaptic hotspots for establishment of new functional excitatory synapses.
منابع مشابه
An LRRTM4-HSPG Complex Mediates Excitatory Synapse Development on Dentate Gyrus Granule Cells
Selective synapse development determines how complex neuronal networks in the brain are formed. Complexes of postsynaptic neuroligins and LRRTMs with presynaptic neurexins contribute widely to excitatory synapse development, and mutations in these gene families increase the risk of developing psychiatric disorders. We find that LRRTM4 has distinct presynaptic binding partners, heparan sulfate p...
متن کاملPostsynaptic TrkC and Presynaptic PTPσ Function as a Bidirectional Excitatory Synaptic Organizing Complex
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 differen...
متن کاملExogenous MPP3 is Sufficient to Induce Excitatory Synapse Formation
Brain-derived neurotrophic factor (BDNF) is a secreted growth factor critical for the establishment and maintenance of central nervous system (CNS) synapses. However, the precise mechanisms that allow BDNF signaling to regulate synapse formation are unknown. Interestingly, MAGUK scaffold proteins, a family of proteins critical for organizing the molecular architecture of the synapse, have alter...
متن کاملThe Arp2/3 Complex Is Essential for Distinct Stages of Spine Synapse Maturation, Including Synapse Unsilencing.
UNLABELLED Dendritic filopodia are actin-rich structures that are thought to contribute to early spine synapse formation; however, the actin regulatory proteins important for early synaptogenesis are poorly defined. Using organotypic hippocampal slice cultures and primary neuron hippocampal cultures from Arp2/3 conditional knock-out mice, we analyze the roles of the Arp2/3 complex, an actin reg...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Neuron
دوره 49 شماره
صفحات -
تاریخ انتشار 2006