vesl, a gene encoding VASP/Ena family related protein, is upregulated during seizure, long‐term potentiation and synaptogenesis¹

Abstract

We have isolated a novel cDNA, vesl, that was induced during convulsive seizure in the rat hippocampus. The vesl gene encodes a protein of 186 amino acids that has significant homology to the EVH1 domain of the VASP/Ena family of proteins implicated in the control of microfilament dynamics. The expression of vesl mRNA was induced in the granule cell layer during persistent long-term potentiation (LTP) of the dentate gyrus in an NMDA receptor-dependent manner. Furthermore, vesl mRNA was expressed at a high level during hippocampal synaptogenesis. We suggest that the Vesl protein may be involved in the structural changes that occur at synapses during long-lasting neuronal plasticity and development.© 1997 Federation of European Biochemical Societies.Key words: Long-term potentiation; Seizure; Hippocampus; Gene regulation; PCR differential display IntroductionBehavioral and pharmacological studies have revealed that memory has at least two distinct components, short-term and long-term memory. Long-term memory differs from shortterm memory in that it requires gene expression and protein synthesis at a critical period during and/or shortly after the learning experience (for review, [3]). Various protein synthesis inhibitors block the prolonged storage of memory without affecting short-term memory, in both vertebrates and invertebrates. This suggests that gene products synthesized during learning switch the stored information from a short-lasting labile form to a long-lasting stable form [4].Activity-dependent changes in the strength of synaptic transmission have been considered to provide a plausible cellular basis for learning and memory. Long-term potentiation (LTP) is a typical form of synaptic plasticity, in which elec-*Corresponding author. Fax: (81) (427) trical stimulation causes a long-lasting increase in synaptic efficacy [5]. Importantly, LTP in the hippocampus appears to have two distinct phases. The early phase, which persists ~ 3 h, is independent of macromolecule synthesis, whereas the late phase, which lasts for several hours in vitro and even for weeks in vivo, is prevented by pharmacological inhibition of protein and RNA synthesis, without any effects on the early phase [6][7][8][9][10]. These results strongly suggest that a particular set of genes, whose expression is induced after neural activity, play crucial roles in the prolonged maintenance of plastic changes in synaptic efficacy. Recent studies have identified a number of genes that are induced following a high-frequency stimulus (HFS) that elicits the late phase of LTP [11][12][13][14][15][16][17][18][19][20]. A major class of genes identified so far encodes transcription factors such as NGFI-A (also called Zif268, Krox24 and Egrl), c-Fos, Krox20 (Egr2), and Egr3 [11,12,16,20], supporting the hypothesis that altered gene expression is a prerequisite for the prolonged maintenance of LTP. In addition to these regulatory proteins, the late phase of LTP is accompanied by the induction of effector proteins such as activin [3A and Arc [1...

Ontogeny of postsynaptic density proteins at glutamatergic synapses

“…2,9, Table 1). Homer 1a has been described during development; mRNA for the latter is present in the early postnatal hippocampus and peaks at P14 (Kato et al, 1997). However, since Homer 1a is an immediate early gene product and lacks the coiled-coil domain needed for Homer dimerization, its distribution may not coincide with that of other Homers such as the 1b,c form studied here.…”

Homer1/mGluR5 Activity Moderates Vulnerability to Chronic Social Stress

“…Activation of Homer1a gene transcription is a rapid and plastic process in response to synaptic activity (de Bartolomeis and Iasevoli, 2003;Brakeman et al, 1997;Kato et al, 1997). It can be hypothesized that repeated transcriptional activation of this immediate early gene in response to the daily defeat sessions induces counter-regulatory changes in the central stress systems, including the upregulation of Homer1b/c (Berton et al, 2006).…”

Mathematical modeling of noise and discovery of genetic expression classes in gliomas

“…Clone 162646, up-regulated in GBM, is homologous to the Ana/VASP protein family that is implicated to be involved in the control of cell motility through actin filament assembly of their GP5 motifs (Ohta et al, 1997). Members of this family are upregulated during seizures and long-term potentiation (Kato et al, 1997). Clone 280244 (Class 1b) is 54% similar to testican, a putative extracellular heparan/ chondroitin sulfate proteoglycan expressed in a variety of human tissues but is most abundant in brain (Marr et al, 2000).…”