Biochemical Society Transactions

Published by Portland Press
Online ISSN: 1470-8752
Print ISSN: 0300-5127
The present paper describes concisely the expression and role of α(1,2)-linked fucose on some glycoconjugates as well as the detection, distribution and potential role of that glycotope on human soluble plasma and cellular fibronectins in addition to the expression on both normal and pathological amniotic fluid and seminal plasma fibronectins. The determination of α(1,2)fucosylated glycans is considered with respect to its usefulness as a potential clinically applicable biomarker in obstetrics to monitor pregnancy and in andrology to evaluate the ejaculate of infertile men and in vitro fertilization.
Activation of InsP(3)Rs (InsP(3) receptors) represents the major mechanism underlying intracellular calcium release in non-excitable cells such as hepatocytes and exocrine cells from the pancreas and salivary glands. Modulation of calcium release through InsP(3)Rs is therefore a major route whereby the temporal and spatial characteristics of calcium waves and oscillations can potentially be 'shaped'. In this study, the functional consequences of phosphoregulation of InsP(3)Rs were investigated. Pancreatic and parotid acinar cells express all three types of InsP(3)R in differing abundance, and all are potential substrates for phosphoregulation. PKA (protein kinase A)-mediated phosphorylation of InsP(3)Rs in pancreatic acinar cells resulted in slowed kinetics of calcium release following photo-release of InsP(3). In contrast, activation of PKA in parotid cells resulted in a marked potentiation of calcium release. In pancreatic acinar cells the predominant InsP(3)R isoform phosphorylated was the type 3 receptor, while the type 2 receptor was markedly phosphorylated in parotid acinar cells. In order to further decipher the effects of phosphorylation on individual InsP(3)R subtypes, DT-40 cell lines expressing homotetramers of a single isoform of InsP(3)R were utilized. These data demonstrate that phosphoregulation of InsP(3)Rs results in subtype-specific effects and may play a role in the specificity of calcium signals by 'shaping' the spatio-temporal profile of the response.
In this review we speculate that the anti-apoptotic protein Bcl-2 may regulate calcium signals involved in mediating cell death. Evidence that Ins(1,4,5)P(3)-mediated calcium release from the endoplasmic reticulum triggers apoptosis in response to diverse signals is summarized. Also, we review evidence that Bcl-2 regulates calcium release from the endoplasmic reticulum, and speculate that Bcl-2 may interact either functionally or physically with Ins(1,4,5)P(3) receptors to modulate calcium signals that determine life or death decisions.
Starfish oocytes that are extracted from the ovaries are arrested at the prophase of the first meiotic division. At this stage of maturation, they are characterized by a large nucleus called the germinal vesicle. Meiosis resumption (maturation) can be induced in vitro by adding the hormone 1-methyladenine (1-MA) to the seawater in which the oocytes are suspended. Earlier work in our laboratory had detected Ca(2+) increases in both the cytoplasm and the nucleus of the oocytes approx. 2 min after the 1-MA challenge. The nuclear Ca(2+) increase was found to be essential for the continuation of the meiotic cycle, since the injection of bis-(o-aminophenoxy)ethane- N,N,N',N' -tetra-acetic acid (BAPTA) into the nuclear compartment completely blocked the re-initiation of the cell cycle. We have recently confirmed, using confocal microscopy, that the cytoplasmic and nuclear Ca(2+) pools are regulated independently and that the nuclear envelope in starfish oocytes is not freely permeated by the Ca(2+) wave that sweeps across the nuclear region. Studies by others have shown that the sensitivity of the Ins(1,4,5) P (3) (IP(3)) receptors (IP(3)Rs) to IP(3) increases during oocyte maturation, so that they release progressively more calcium in response to the injection of IP(3), as maturation proceeds. We have now shown that the increased sensitivity of the IP(3)Rs may depend on the activation of the cyclin-dependent kinase, MPF (M-phase-promoting factor) that occurs in the nucleus. MPF does not directly phosphorylate IP(3)Rs but phosphorylates instead the actin-binding protein actin depolymerization factor (ADF)/cofilin.
Top-cited authors
Hartmut Lichtenthaler
  • Karlsruhe Institute of Technology
David Komander
  • The Walter and Eliza Hall Institute of Medical Research
Jingxiang Huang
  • National University Health System
Mary Mccaffrey
  • University College Cork
Paul J Thornalley
  • Hamad bin Khalifa University