PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 11075829

Structure-function relations in dendritic spines: is size important?

E Korkotian·M Segal
View original source ↗Export metadata ↓

Abstract

The recent use of novel high-resolution imaging methods of living neurons in vitro has led to a change in the view of the dendritic spine, from a stable, long-term memory storage device to that of a dynamic structure, which can undergo fast morphological changes over periods of hours and even minutes. While the functional significance of these changes in spine dimensions is still obscure, we have obtained evidence to indicate that the length of the spine has a critical role in determining the degree of interaction between the spine head and the parent dendrite, such that longer spines are more independent of the parent dendrite than the short ones. We have now studied the role of intracellular calcium stores in determining the magnitude and time course of spine responses to a calcium surge evoked in response to glutamate, which causes an influx of calcium, and the results indicate that spine morphology has an important role in determining the involvement of the stores in calcium responses. Since spines can change their length over a rather short time, these results indicate that changes in spine length serve to fine-tune the interaction between the spine head and the parent dendrite on a continuous basis.

Explore related subjects

CalciumCalcium SignalingCells, CulturedDendritesGlutamic AcidHippocampusIntracellular MembranesNeuronal PlasticityJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

E Korkotian, M Segal. 2000. Structure-function relations in dendritic spines: is size important?. https://doi.org/10.1002/1098-1063(2000)10%3A5%3C587%3A%3Aaid-hipo9%3E3.0.co%3B2-c

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2003

The catalytic domain limits the translocation of protein kinase C alpha in response to increases in Ca2+ and diacylglycerol.

Translocation of protein kinase C (PKC) alpha, beta II, delta and epsilon fused to enhanced green fluorescent protein (EGFP) was studied in living neuroblastoma cells by confocal microscopy. Exposure to carbachol elicited transient translocation of PKC alpha-EGFP and beta II-EGFP in most of the cells, PKC delta-EGFP in a few cells and induced sustained translocation of PKC epsilon-EGFP. To monitor levels of Ca(2+) and diacylglycerol and the translocation of PKC in the same cell, the Ca(2+)-sensitive C2 domain, diacylglycerol-sensitive C1 domains and full-length PKC were fused to red, cyan and yellow fluorescent proteins respectively. PKC alpha was translocated a few seconds after the C2 domain, which represents an increase in Ca(2+). This delay was insensitive to removal of the pseudosubstrate in PKC alpha, but the isolated regulatory domain translocated simultaneously with the C2 domain. Translocation of PKC epsilon coincided with the increase in diacylglycerol. Ionomycin induced translocation of PKC alpha and the C2 domain, whereas 1,2-dioctanoylglycerol caused translocation of the C1 domains and PKC epsilon, but not PKC alpha. Experiments with individual C1 domains showed that treatment with carbachol or phorbol 12,13-dibutyrate elicited translocation of PKC alpha C1a, PKC epsilon C1a and PKC epsilon C1b, whereas PKC alpha C1b was largely insensitive to these agents. In contrast with full-length PKC alpha, the regulatory domain of PKC alpha and pseudosubstrate-devoid PKC alpha responded to the carbachol-stimulated increase in diacylglycerol.

Calcium↗
PubMed2003

Activation of S6K1 (p70 ribosomal protein S6 kinase 1) requires an initial calcium-dependent priming event involving formation of a high-molecular-mass signalling complex.

The mitogen-stimulated protein kinase p70 ribosomal protein S6 kinase 1 (S6K1) is a key enzyme in the regulation of cell growth and proliferation. Activation of S6K1 requires a complex, ordered series of conformational changes and phosphorylation reactions. While the role of sequential, multi-site phosphorylation has been extensively detailed, characterization of the priming step required to initiate this cascade has remained elusive. In the present study we show for the first time that this priming process is dependent on calcium. Calcium-dependent regulation of S6K1 did not specifically target Thr-229 and Thr-389, the key regulatory phosphorylation sites; rather, calcium chelation resulted in a global inhibition of S6K1 phosphorylation. Mutation of individual phosphorylation sites in the auto-inhibitory and hydrophobic domains to acidic residues (to mimic phosphorylation) yields a kinase that remains sensitive to calcium chelation, while the combined mutations alleviate the requirement for calcium. Furthermore, deletion of the C-terminal residues (398-502) also renders the kinase insensitive to calcium. We hypothesize that the initial calcium-dependent process is required to release an inhibitory interaction between the C- and N-termini of S6K1, thus allowing phosphorylation of these key domains. The requirement for this priming step can only be overcome by mutations mimicking the phosphorylation of both the auto-inhibitory and hydrophobic domains. We further propose that the priming event involves formation of a calcium-dependent protein complex that releases the interaction between the N- and C-termini. S6K1 is then accessible for activation by the kinases that target the known regulatory phosphorylation sites. Consistent with this hypothesis, serum stimulation of S6K1 activity is associated with its incorporation into a calcium-dependent high-molecular-mass complex.

Calcium↗