Sense and specificity in neuronal calcium signalling

AbstractChanges in the intracellular free calcium concentration ([Ca2+]i) in neurons regulate many and varied aspects of neuronal function over time scales from microseconds to days. The mystery is how a single signalling ion can lead to such diverse and specific changes in cell function. This is partly due to aspects of the Ca2+ signal itself, including its magnitude, duration, localisation and persistent or oscillatory nature. The transduction of the Ca2+ signal requires Ca2+ binding to various Ca2+ sensor proteins. The different properties of these sensors are important for differential signal processing and determine the physiological specificity of Ca2+ signalling pathways. A major factor underlying the specific roles of particular Ca2+ sensor proteins is the nature of their interaction with target proteins and how this mediates unique patterns of regulation. We review here recent progress from structural analyses and from functional analyses in model organisms that have begun to reveal the rules that underlie Ca2+ sensor protein specificity for target interaction. We discuss three case studies exemplifying different aspects of Ca2+ sensor/target interaction. This article is part of a special issue titled the 13th European Symposium on Calcium

Neuronal calcium sensor proteins: emerging roles in membrane traffic and synaptic plasticity

Ca2+ plays a crucial role in the regulation of neuronal function. Recent work has revealed important functions for two families of neuronally expressed Ca2+ sensor proteins. These include roles in membrane traffic and in alterations in synaptic plasticity underlying changes in behaviour

Acoustic comfort in open-plan offices: The role of employee characteristics

Purpose – This paper aims to determine the extent to which employees’ experiences of acoustic comfort, well-being and productivity in open-plan offices are determined by specific characteristics (including demographic information, task characteristics, and personality traits). Design/methodology/approach – A questionnaire was distributed to the occupants of three open-plan office sites and was completed by 166 employees in total. Findings – The results indicated that acoustic comfort in open-plan offices is largely determined by noise sensitivity. Higher noise sensitivity was associated with more negative ratings of acoustical quality, more perceived disturbance by speech and more difficulties in concentration. More negative experiences were also reported by employees with lower interactivity with colleagues. Practical implications – There is significant inter-individual variability in experiences of acoustic comfort, well-being and productivity in open-plan offices. As such, workplace practitioners should consider acoustic and behavioural solutions for introducing a greater diversity of functional workspaces within the office, so that employees can choose the most suitable working area for their requirements. Originality/value – Whereas the majority of past acoustics research has been laboratory-based, this study is conducted in real office environments with a representative sample of knowledge workers

Evolution and functional diversity of the Calcium Binding Proteins (CaBPs)

The mammalian central nervous system (CNS) exhibits a remarkable ability to process, store, and transfer information. Key to these activities is the use of highly regulated and unique patterns of calcium signals encoded by calcium channels and decoded by families of specific calcium-sensing proteins. The largest family of eukaryotic calcium sensors is those related to the small EF-hand containing protein calmodulin (CaM). In order to maximize the usefulness of calcium as a signaling species and to permit the evolution and fine tuning of the mammalian CNS, families of related proteins have arisen that exhibit characteristic calcium binding properties and tissue-, cellular-, and sub-cellular distribution profiles. The Calcium Binding Proteins (CaBPs) represent one such family of vertebrate specific CaM like proteins that have emerged in recent years as important regulators of essential neuronal target proteins. Bioinformatic analyses indicate that the CaBPs consist of two subfamilies and that the ancestral members of these are CaBP1 and CaBP8. The CaBPs have distinct intracellular localizations based on different targeting mechanisms including a novel type-II transmembrane domain in CaBPs 7 and 8 (otherwise known as calneuron II and calneuron I, respectively). Recent work has led to the identification of new target interactions and possible functions for the CaBPs suggesting that they have multiple physiological roles with relevance for the normal functioning of the CNS

Determination of the Membrane Topology of the Small EF-Hand Ca2+-Sensing Proteins CaBP7 and CaBP8

The CaBPs represent a subfamily of small EF-hand containing calcium (Ca2+)-sensing proteins related to calmodulin that regulate key ion channels in the mammalian nervous system. In a recent bioinformatic analyses we determined that CaBP7 and CaBP8 form an evolutionarily distinct branch within the CaBPs (also known as the calneurons) a finding that is consistent with earlier observations characterising a putative C-terminal transmembrane (TM) spanning helix in each of these proteins which is essential for their sub-cellular targeting to the Golgi apparatus and constitutive secretory vesicles. The C-terminal position of the predicted TM-helix suggests that CaBP7 and CaBP8 could be processed in a manner analogous to tail-anchored integral membrane proteins which exhibit the ability to insert across membranes post-translationally. In this study we have investigated the topology of CaBP7 and CaBP8 within cellular membranes through a combination of trypsin protection and epitope accessibility analyses. Our results indicate that the TM-helices of CaBP7 and CaBP8 insert fully across membranes such that their extreme C-termini are luminal. The observed type-II membrane topology is consistent with processing of CaBP7 and CaBP8 as true tail-anchored proteins. This targeting mechanism is distinct from any other calmodulin related Ca2+-sensor and conceivably underpins unique physiological functions of these proteins

The frequency and properties of young tidal dwarf galaxies in nearby gas-rich groups

We present high-resolution Giant Metrewave Radio Telescope (GMRT) HI observations and deep Canada-France-Hawaii Telescope (CFHT) optical imaging of two galaxy groups: NGC 4725/47 and NGC 3166/9. These data are part of a multi-wavelength unbiased survey of the gas-rich dwarf galaxy populations in three nearby interacting galaxy groups. The NGC 4725/47 group hosts two tidal knots and one dIrr. Both tidal knots are located within a prominent HI tidal tail, appear to have sufficient mass (M_gas~10^8 M_sol) to evolve into long-lived tidal dwarf galaxies (TDGs) and are fairly young in age. The NGC 3166/9 group contains a TDG candidate, AGC 208457, at least three dIrrs and four HI knots. Deep CFHT imaging confirms that the optical component of AGC 208457 is bluer -- with a 0.28 mag g-r colour -- and a few Gyr younger than its purported parent galaxies. Combining the results for these groups with those from the NGC 871/6/7 group reported earlier, we find that the HI properties, estimated stellar ages and baryonic content of the gas-rich dwarfs clearly distinguish tidal features from their classical counterparts. We optimistically identify four potentially long-lived tidal objects associated to three separate pairs of interacting galaxies, implying that TDGs are not readily produced during interaction events as suggested by some recent simulations. The tidal objects examined in this survey also appear to have a wider variety of properties than TDGs of similar mass formed in current simulations of interacting galaxies, which could be the result of pre- or post-formation environmental influences.Comment: 18 pages, 14 figures, accepted for publication in MNRA

Modulation of phosphatidylinositol 4-phosphate levels by CaBP7 controls cytokinesis in mammalian cells

Calcium and phosphoinositide signaling regulate cell division in model systems, but their significance in mammalian cells is unclear. Calcium-binding protein-7 (CaBP7) is a phosphatidylinositol 4-kinaseIIIβ (PI4KIIIβ) inhibitor required during cytokinesis in mammalian cells, hinting at a link between these pathways. Here we characterize a novel association of CaBP7 with lysosomes that cluster at the intercellular bridge during cytokinesis in HeLa cells. We show that CaBP7 regulates lysosome clustering and that PI4KIIIβ is essential for normal cytokinesis. CaBP7 depletion induces lysosome mislocalization, extension of intercellular bridge lifetime, and cytokinesis failure. These data connect phosphoinositide and calcium pathways to lysosome localization and normal cytokinesis in mammalian cells

Gas, Stars, and Star Formation in ALFALFA Dwarf Galaxies

We examine the global properties of the stellar and H I components of 229 low H_I mass dwarf galaxies extracted from the ALFALFA survey, including a complete sample of 176 galaxies with H_I masses <10^(7.7) M_☉ and H_I line widths <80 km s^(–1). Sloan Digital Sky Survey (SDSS) data are combined with photometric properties derived from Galaxy Evolution Explorer to derive stellar masses (M_*) and star formation rates (SFRs) by fitting their UV-optical spectral energy distributions (SEDs). In optical images, many of the ALFALFA dwarfs are faint and of low surface brightness; only 56% of those within the SDSS footprint have a counterpart in the SDSS spectroscopic survey. A large fraction of the dwarfs have high specific star formation rates (SSFRs), and estimates of their SFRs and M_* obtained by SED fitting are systematically smaller than ones derived via standard formulae assuming a constant SFR. The increased dispersion of the SSFR distribution at M_* ≲ 10^8 M_☉ is driven by a set of dwarf galaxies that have low gas fractions and SSFRs; some of these are dE/dSphs in the Virgo Cluster. The imposition of an upper H_I mass limit yields the selection of a sample with lower gas fractions for their M_* than found for the overall ALFALFA population. Many of the ALFALFA dwarfs, particularly the Virgo members, have H_I depletion timescales shorter than a Hubble time. An examination of the dwarf galaxies within the full ALFALFA population in the context of global star formation (SF) laws is consistent with the general assumptions that gas-rich galaxies have lower SF efficiencies than do optically selected populations and that H_I disks are more extended than stellar ones