title: Change in the shape and density of dendritic spines caused by overexpression of acidic calponin in cultured hippocampal neurons.
abstract: Dendritic spines are morphing structures believed to provide a cellular substrate for synaptic plasticity. It has been suggested that the actin cytoskeleton is the target of molecular mechanisms regulating spine morphology. Here we hypothesized that acidic calponin, an actin-binding protein, is one of the key regulators of actin filaments during spine plasticity. Our data showed that the overexpression of acidic calponin-GFP (green fluorescent protein) in primary cultures of rat hippocampal neurons causes an elongation of spines and an increase of their density as compared with those of GFP-expressing neurons. These effects required the actin-binding domains of acidic calponin. The close apposition of the presynatic marker synaptophysin to these long spines and the presence of specific postsynaptic markers actin, PSD-95, NR1, and GluR1 suggested the existence of functional excitatory synaptic contacts. Indeed, electrophysiological data showed that the postsynaptic overexpression of acidic calponin enhanced the frequency of miniature excitatory postsynaptic currents as compared with that of GFP-expressing neurons, but did not affect their properties such as amplitude, rise time, and half width. Studies in heterologous cells revealed that acidic calponin reorganized the actin filaments and stabilized them. Taken together, these findings show that acidic calponin regulates dendritic spine morphology and density, likely via regulation of the actin cytoskeleton reorganization and dynamic. Furthermore, the acidic calponin-induced spines are able to establish functional glutamatergic synapses. Such data suggest that acidic calponin is a key factor in the regulation of spine plasticity and synaptic activity.
authors.affiliation: INMED/INSERM U29, 163 rue de Luminy, BP 13, 13273, Marseille Cedex 09, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Rami
authors.forename: Olivier
authors.initials: O
authors.lastname: Caillard
authors.forename: Igor
authors.initials: I
authors.lastname: Medina
authors.forename: Christophe
authors.initials: C
authors.lastname: Pellegrino
authors.forename: Abdellatif
authors.initials: A
authors.lastname: Fattoum
authors.forename: Yezekiel
authors.initials: Y
authors.lastname: Ben-Ari
authors.forename: Lotfi
authors.initials: L
authors.lastname: Ferhat
mesh_terms: D000199:Actins / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D000906:Antibodies / Q000276:immunology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D016466:CHO Cells; D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics*; D002478:Cells, Cultured; D006224:Cricetinae; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D049229:Dendritic Spines / Q000502:physiology* / Q000648:ultrastructure*; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D007091:Image Processing, Computer-Assisted; D008840:Microfilament Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure*; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D014162:Transfection; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology; D000096985:Calponins
chemical_list: D000199:Actins; D000906:Antibodies; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002135:Calcium-Binding Proteins; D018076:DNA, Complementary; D049452:Green Fluorescent Proteins; D008840:Microfilament Proteins; D013844:Thiazoles; D053778:Thiazolidines; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D000096985:Calponins; C037068:latrunculin B