A preformed complex of postsynaptic proteins is involved in excitatory synapse development.
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.
Department of Psychiatry and the Brain Research Centre, University of British Columbia, Vancouver, British Columbia, Canada, V6T 1Z3.
Kimberly
K
Gerrow
Stefano
S
Romorini
Shahin M
SM
Nabi
Michael A
MA
Colicos
Carlo
C
Sala
Alaa
A
El-Husseini
D000199:Actins / Q000502:physiology; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal; D002478:Cells, Cultured; D003952:Diagnostic Imaging / Q000379:methods; D000076122:Disks Large Homolog 4 Protein; D054637:Dual-Specificity Phosphatases; D004622:Embryo, Mammalian; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D007150:Immunohistochemistry / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000145:classification / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000166:cytology*; D015739:Nocodazole / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000502:physiology*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology; D021381:Protein Transport / Q000187:drug effects; D011726:Pyridinium Compounds / Q000493:pharmacokinetics; D000644:Quaternary Ammonium Compounds / Q000493:pharmacokinetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000502:physiology*; D013997:Time Factors; D050496:Vesicular Glutamate Transport Proteins / Q000378:metabolism
D000199:Actins; D015816:Cell Adhesion Molecules, Neuronal; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; C092350:FM 4-64; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D034741:RNA, Small Interfering; D050496:Vesicular Glutamate Transport Proteins; C093438:neuroligin 1; C033652:postsynaptic density proteins; D049452:Green Fluorescent Proteins; D010749:Phosphoprotein Phosphatases; C489855:dual specificity phosphatase 12; D054637:Dual-Specificity Phosphatases; D015739:Nocodazole