title: The actin-binding protein profilin I is localized at synaptic sites in an activity-regulated manner.
abstract: Morphological changes at synaptic specializations have been implicated in regulating synaptic strength. Actin turnover at dendritic spines is regulated by neuronal activity and contributes to spine size, shape and motility. The reorganization of actin filaments requires profilins, which stimulate actin polymerization. Neurons express two independent gene products - profilin I and profilin II. A role for profilin II in activity-dependent mechanisms at spine synapses has recently been described. Although profilin I interacts with synaptic proteins, little is known about its cellular and subcellular localization in neurons. Here, we investigated the subcellular distribution of this protein in brain neurons as well as in hippocampal cultures. Our results indicate that the expression of profilin I varies in different brain regions. Thus, in cerebral cortex and hippocampus profilin I immunostaining was associated predominantly with dendrites and was present in a subset of dendritic spines. In contrast, profilin I in cerebellum was associated primarily with presynaptic structures. Profilin I immunoreactivity was partially colocalized with the synaptic molecules synaptophysin, PSD-95 and gephyrin in cultured hippocampal neurons, indicating that profilin I is present in only a subset of synapses. At dendritic spine structures, profilin I was found primarily in protrusions, which were in apposition to presynaptic terminal boutons. Remarkably, depolarization with KCl caused a moderate but significant increase in the number of synapses containing profilin I. These results show that profilin I can be present at both pre- and postsynaptic sites and suggest a role for this actin-binding protein in activity-dependent remodelling of synaptic structure.
authors.affiliation: Zentrum für Molekulare Neurobiologie Hamburg, ZMNH, University of Hamburg, Falkenried 94, D-20251 Hamburg, Germany. matthias.kneussel@zmnh.uni-hamburg.de
authors.forename: Henrike
authors.initials: H
authors.lastname: Neuhoff
authors.forename: Marco
authors.initials: M
authors.lastname: Sassoè-Pognetto
authors.forename: Patrizia
authors.initials: P
authors.lastname: Panzanelli
authors.forename: Christoph
authors.initials: C
authors.lastname: Maas
authors.forename: Walter
authors.initials: W
authors.lastname: Witke
authors.forename: Matthias
authors.initials: M
authors.lastname: Kneussel
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002478:Cells, Cultured; D003285:Contractile Proteins / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D000076122:Disks Large Homolog 4 Protein; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D051528:Guanylate Kinases; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism*; D016253:Microscopy, Immunoelectron / Q000379:methods; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology*; D051304:Profilins; D018709:Statistics, Nonparametric; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D016708:Synaptophysin / Q000378:metabolism; D051178:alpha Catenin
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003285:Contractile Proteins; C495272:Ctnna1 protein, mouse; D003598:Cytoskeletal Proteins; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; C495739:Pfn1 protein, mouse; C495742:Pfn2 protein, mouse; D051304:Profilins; D016708:Synaptophysin; D051178:alpha Catenin; C073441:gephyrin; C033652:postsynaptic density proteins; D049452:Green Fluorescent Proteins; D011189:Potassium Chloride; D051528:Guanylate Kinases