title: Reggie-1 and reggie-2 (flotillins) participate in Rab11a-dependent cargo trafficking, spine synapse formation and LTP-related AMPA receptor (GluA1) surface exposure in mouse hippocampal neurons.
abstract: Reggie-1 and -2 (flotillins) reside at recycling vesicles and promote jointly with Rab11a the targeted delivery of cargo. Recycling is essential for synapse formation suggesting that reggies and Rab11a may regulate the development of spine synapses. Recycling vesicles provide cargo for dendritic growth and recycle surface glutamate receptors (AMPAR, GluA) for long-term potentiation (LTP) induced surface exposure. Here, we show reduced number of spine synapses and impairment of an in vitro correlate of LTP in hippocampal neurons from reggie-1 k.o. (Flot2-/-) mice maturating in culture. These defects apparently result from reduced trafficking of PSD-95 revealed by live imaging of 10 div reggie-1 k.o. (Flot2-/-) neurons and likely impairs co-transport of cargo destined for spines: N-cadherin and the glutamate receptors GluA1 and GluN1. Impaired cargo trafficking and fewer synapses also emerged in reggie-1 siRNA, reggie-2 siRNA, and reggie-1 and -2 siRNA-treated neurons and was in siRNA and k.o. neurons rescued by reggie-1-EGFP and CA-Rab11a-EGFP. While correlative expressional changes of specific synapse proteins were observed in reggie-1 k.o. (Flot2-/-) brains in vivo, this did not occur in neurons maturating in vitro. Our work suggests that reggie-1 and reggie-2 function at Rab11a recycling containers in the transport of PSD-95, N-cadherin, GluA1 and GluN1, and promote (together with significant signaling molecules) spine-directed trafficking, spine synapse formation and the in vitro correlate of LTP.
authors.affiliation: Dept. Biology, University Konstanz, 78464 Konstanz, Germany. Electronic address: Vsevolod.Bodrikov@uni-konstanz.de.
authors.forename: Vsevolod
authors.initials: V
authors.lastname: Bodrikov
authors.affiliation: Dept. Biology, University Konstanz, 78464 Konstanz, Germany. Electronic address: AlinePauschert@web.de.
authors.forename: Aline
authors.initials: A
authors.lastname: Pauschert
authors.affiliation: Leibniz-Institut für Molekulare Pharmakologie, Robert-Roessle-Straße 10, 13125 Berlin, Germany. Electronic address: kochlamazashvili@fmp-berlin.de.
authors.forename: Gaga
authors.initials: G
authors.lastname: Kochlamazashvili
authors.affiliation: Dept. Biology, University Konstanz, 78464 Konstanz, Germany. Electronic address: Claudia.Stuermer@uni-konstanz.de.
authors.forename: Claudia A O
authors.initials: CAO
authors.lastname: Stuermer
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015820:Cadherins / Q000378:metabolism; D002478:Cells, Cultured; D000076122:Disks Large Homolog 4 Protein; D004705:Endocytosis / Q000187:drug effects / Q000235:genetics; D005260:Female; D051528:Guanylate Kinases / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D021381:Protein Transport / Q000235:genetics; D011726:Pyridinium Compounds / Q000493:pharmacokinetics; D000644:Quaternary Ammonium Compounds / Q000493:pharmacokinetics; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013997:Time Factors; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
chemical_list: D015820:Cadherins; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D034741:RNA, Small Interfering; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C501447:Dlg4 protein, mouse; C092350:FM 4-64; C121673:Gprin1 protein, mouse; C106354:flotillins
keywords: Correlative expressional changes; In vitro correlate of LTP; Knock out mice; Lipid raft; Rab11a; Recycling; Reggie (flotillin); Spine synapses; Synaptic plasticity