Synaptopodin regulates plasticity of dendritic spines in hippocampal neurons.
The spine apparatus is an essential component of dendritic spines of cortical and hippocampal neurons, yet its functions are still enigmatic. Synaptopodin (SP), an actin-binding protein, is tightly associated with the spine apparatus and it may play a role in synaptic plasticity, but it has not yet been linked mechanistically to synaptic functions. We studied endogenous and transfected SP in dendritic spines of cultured hippocampal neurons and found that spines containing SP generate larger responses to flash photolysis of caged glutamate than SP-negative ones. An NMDA-receptor-mediated chemical long-term potentiation caused the accumulation of GFP-GluR1 in spine heads of control but not of shRNA-transfected, SP-deficient neurons. SP is linked to calcium stores, because their pharmacological blockade eliminated SP-related enhancement of glutamate responses, and release of calcium from stores produced an SP-dependent increase of GluR1 in spines. Thus, SP plays a crucial role in the calcium store-associated ability of neurons to undergo long-term plasticity.
Vlachos
Andreas
A
Department of Neurobiology, The Weizmann Institute, Rehovot 76100, Israel.
Korkotian
Eduard
E
Schonfeld
Eldi
E
Copanaki
Ekaterini
E
Deller
Thomas
T
Segal
Menahem
M
D000082:Acetaminophen / Q000494:pharmacology; D000199:Actins / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D000983:Antipyrine / Q000031:analogs & derivatives / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003061:Codeine / Q000494:pharmacology; D049229:Dendritic Spines / Q000187:drug effects / Q000502:physiology*; D004338:Drug Combinations; D004558:Electric Stimulation / Q000379:methods; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology*; D008840:Microfilament Proteins / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D018408:Patch-Clamp Techniques / Q000379:methods; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism; D014162:Transfection / Q000379:methods
D000082:Acetaminophen; D000199:Actins; D000983:Antipyrine; D002110:Caffeine; D002118:Calcium; D003061:Codeine; D004338:Drug Combinations; D018683:Excitatory Amino Acid Agents; D049452:Green Fluorescent Proteins; D008840:Microfilament Proteins; D034741:RNA, Small Interfering; D018091:Receptors, AMPA; D019837:Ryanodine Receptor Calcium Release Channel; D016708:Synaptophysin; C503969:Synpo protein, rat; C106429:caffeine, codeine, acetaminophen, propyphenazone drug combination; C485184:enhanced green fluorescent protein