The lifetime of inositol 1,4,5-trisphosphate in single cells.

Wang, Samuel Sheng-Hung; Alousi, Adawia A.; Thompson, Stuart H.

doi:10.1085/jgp.105.1.149

Cited by 107 publications

(77 citation statements)

References 58 publications

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“…The cell size is a ∼ 10 μm, the dissociation constant is as small as (33), the dissociation rate is μ ∼ 0.001 s −1 (34), and the EGF diffusion constant is D ∼ 50 μm 2 s −1 (35). The turnover rate of IP3 is estimated as ν ∼ 0.1 s −1 (36). Thus, τ 1 ∼ 15 min, τ 2 ∼ 10 s, and the exchange time of IP3 among cells is τ 3 ∼ 1 s (37) (it is slower than the diffusion in the cytoplasm would allow due to bottlenecks at gap junctions).…”

Section: Discussionmentioning

confidence: 99%

Limits to the precision of gradient sensing with spatial communication and temporal integration

Mugler

Levchenko

Nemenman

2016

Proc. Natl. Acad. Sci. U.S.A.

136

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Gradient sensing requires at least two measurements at different points in space. These measurements must then be communicated to a common location to be compared, which is unavoidably noisy. Although much is known about the limits of measurement precision by cells, the limits placed by the communication are not understood. Motivated by recent experiments, we derive the fundamental limits to the precision of gradient sensing in a multicellular system, accounting for communication and temporal integration. The gradient is estimated by comparing a "local" and a "global" molecular reporter of the external concentration, where the global reporter is exchanged between neighboring cells. Using the fluctuation-dissipation framework, we find, in contrast to the case when communication is ignored, that precision saturates with the number of cells independently of the measurement time duration, because communication establishes a maximum length scale over which sensory information can be reliably conveyed. Surprisingly, we also find that precision is improved if the local reporter is exchanged between cells as well, albeit more slowly than the global reporter. The reason is that whereas exchange of the local reporter weakens the comparison, it decreases the measurement noise. We term such a model "regional excitation-global inhibition." Our results demonstrate that fundamental sensing limits are necessarily sharpened when the need to communicate information is taken into account. C ells sense spatial gradients in environmental chemicals with remarkable precision. A single amoeba, for example, can respond to a difference of roughly 10 attractant molecules between the front and the back of the cell (1). Cells are even more sensitive when they are in a group: Cultures of many neurons respond to chemical gradients equivalent to a difference of only one molecule across an individual neuron's axonal growth cone (2), clusters of malignant lymphocytes have a wider chemotactic sensitivity than single cells (3), and groups of communicating epithelial cells detect gradients that are too weak for a single cell to detect (4). More generally, collective chemosensing properties are often very distinct from those in individual cells (3, 5-7). These observations have generated a renewed interest in the question of what sets the fundamental limit to the precision of gradient sensing in large, spatially extended, often collective sensory systems.Fundamentally, sensing a stationary gradient requires at least two measurements to be made at different points in space. The precision of these two or more individual measurements bounds the gradient sensing precision (8, 9). In its turn, each individual measurement is limited by the finite number of molecules within the detector volume and the ability of the detector to integrate over time, a point first made by Berg and Purcell (BP) (8). More detailed calculations of gradient sensing by specific geometries of receptors have since confirmed that the precision of gradient sensing remains limited by ...

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Section: Discussionmentioning

confidence: 99%

Limits to the precision of gradient sensing with spatial communication and temporal integration

Mugler

Levchenko

Nemenman

2016

Proc. Natl. Acad. Sci. U.S.A.

136

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“…The average lifetimes of cAMP and IP3 in cytoplasm are ∼60 s (Bacskai et al 1993) and <10 s (Kasai and Petersen, 1994;Wang et al, 1995;Fink et al, 1999), respectively. This five-fold difference in lifetime is a major determinant of effective range and steady state concentration of these molecules.…”

Section: Signaling Consequences Of Different Molecular Permeabilitiesmentioning

confidence: 99%

Connexin channel permeability to cytoplasmic molecules

Harris¹

2007

Progress in Biophysics and Molecular Biology

410

346

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Connexin channels are known to be permeable to a variety of cytoplasmic molecules. The first observation of second messenger junctional permeability, made ∼30 years ago, sparked broad interest in gap junction channels as mediators of intercellular molecular signaling. Since then, much has been learned about the diversity of connexin channels with regard to isoform diversity, tissue and developmental distribution, modes of channel regulation, assembly and expression, biochemical modification and permeability, all of which appear to be dynamically regulated. This information has expanded the potential roles of connexin channels in development, physiology and disease, and made their elucidation much more complex -30 years ago such an orchestra of junctional dynamics was unanticipated. Only recently, however, have investigators been able to directly address, in this more complex framework, the key issue: What specific biological molecules, second messengers and others, are able to permeate the various types of connexin channels, and how well? An important related issue, given the ever-growing list of connexin-related pathologies, is how these permeabilities are altered by disease-causing connexin mutations. Together, many studies show that a variety of cytoplasmic molecules can permeate the different types of connexin channels. A few studies reveal differences in permeation by different molecules through a particular type of connexin channel, and differences in permeation by a particular molecule through different types of connexin channels. This article describes and evaluates the various methods used to obtain these data, presents an annotated compilation of the results, and discusses the findings in the context of what can be inferred about mechanism of selectivity and potential relevance to signaling. The data strongly suggest that highly specific interactions take place between connexin pores and specific biological molecular permeants, and that those interactions determine which cytoplasmic molecules can permeate and how well. At this time, the nature of those interactions is unclear. One hopes that with more detailed permeability and structural information, the specific molecular mechanisms of the selectivity can be elucidated.

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“…The parameter values are set as α = 40.0 (s −1 ) , β = 8.0 (s −1 ) and [IP 3 ] max = 5.0 µM (Walker et al, 1987;Wang et al, 1995).…”

Section: Coupled Dynamics Of Camentioning

confidence: 99%

A Cellular Mechanism for Graded Persistent Activity in a Model Neuron and Its Implications in Working Memory

Teramae

Fukai

2005

J Comput Neurosci

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Abstract. Working memory represents the ability of the brain to hold information for relatively short periods of time. Working memory is believed mediated by persistent neuronal firing. A broadly accepted hypothesis is that persistent activity is generated by reverberating synaptic input. However, single cortical neurons capable of showing persistent firing were recently reported. In this modeling study, we propose a cellular mechanism to generate persistent firing of multiple firing rates in single neurons. In the proposed mechanism, bistable concentrations of inositol 1,4,5-trisphosphate (IP 3 ) and Ca 2+ is achieved by IP 3 formation and IP 3 -induced Ca 2+ release from stores in multiple subcellular domains. A postsynaptic firing rate-dependent switching of these bistable elements can demonstrate graded persistent firing of the rat entorhinal neurons. Such a firing rate-dependent switching may be extended to a variety of intracellular Ca 2+ signaling cascades.

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The lifetime of inositol 1,4,5-trisphosphate in single cells.

Cited by 107 publications

References 58 publications

Limits to the precision of gradient sensing with spatial communication and temporal integration

Limits to the precision of gradient sensing with spatial communication and temporal integration

Connexin channel permeability to cytoplasmic molecules

A Cellular Mechanism for Graded Persistent Activity in a Model Neuron and Its Implications in Working Memory

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