Publications by category
Journal articles
Migdalska-Richards A, Smith AR, Richards DM, Schapira AH, Lunnon K (In Press). DNA Methylation of α-Synuclein Intron 1 is Significantly Decreased in the Frontal Cortex of Parkinson’s Individuals with GBA1 Mutations. International Journal of Molecular Sciences
Carmichael R, Richards D, Fahimi HD, Schrader M (In Press). Organelle Membrane Extensions in Mammalian Cells. Biology
Hembrow J, Deeks MJ, Richards DM (2023). Automatic extraction of actin networks in plants.
PLOS Computational Biology,
19(8), e1011407-e1011407.
Abstract:
Automatic extraction of actin networks in plants
The actin cytoskeleton is essential in eukaryotes, not least in the plant kingdom where it plays key roles in cell expansion, cell division, environmental responses and pathogen defence. Yet, the precise structure-function relationships of properties of the actin network in plants are still to be unravelled, including details of how the network configuration depends upon cell type, tissue type and developmental stage. Part of the problem lies in the difficulty of extracting high-quality, quantitative measures of actin network features from microscopy data. To address this problem, we have developed DRAGoN, a novel image analysis algorithm that can automatically extract the actin network across a range of cell types, providing seventeen different quantitative measures that describe the network at a local level. Using this algorithm, we then studied a number of cases in Arabidopsis thaliana, including several different tissues, a variety of actin-affected mutants, and cells responding to powdery mildew. In many cases we found statistically-significant differences in actin network properties. In addition to these results, our algorithm is designed to be easily adaptable to other tissues, mutants and plants, and so will be a valuable asset for the study and future biological engineering of the actin cytoskeleton in globally-important crops.
Abstract.
Richards D, Cockerell A, Wright L, Dattani A, Guo G, Smith A, Tsaneva K (2023). Biophysical models of early mammalian embryogenesis. Stem Cell Reports, 18, 26-46.
Richards DM, Walker JJ, Tabak J (2020). Ion channel noise shapes the electrical activity of endocrine cells.
PLoS Comput Biol,
16(4).
Abstract:
Ion channel noise shapes the electrical activity of endocrine cells.
Endocrine cells in the pituitary gland typically display either spiking or bursting electrical activity, which is related to the level of hormone secretion. Recent work, which combines mathematical modelling with dynamic clamp experiments, suggests the difference is due to the presence or absence of a few large-conductance potassium channels. Since endocrine cells only contain a handful of these channels, it is likely that stochastic effects play an important role in the pattern of electrical activity. Here, for the first time, we explicitly determine the effect of such noise by studying a mathematical model that includes the realistic noisy opening and closing of ion channels. This allows us to investigate how noise affects the electrical activity, examine the origin of spiking and bursting, and determine which channel types are responsible for the greatest noise. Further, for the first time, we address the role of cell size in endocrine cell electrical activity, finding that larger cells typically display more bursting, while the smallest cells almost always only exhibit spiking behaviour.
Abstract.
Author URL.
Passmore JB, Carmichael RE, Schrader TA, Godinho LF, Ferdinandusse S, Lismont C, Wang Y, Hacker C, Islinger M, Fransen M, et al (2020). Mitochondrial fission factor (MFF) is a critical regulator of peroxisome maturation.
Biochim Biophys Acta Mol Cell Res,
1867(7).
Abstract:
Mitochondrial fission factor (MFF) is a critical regulator of peroxisome maturation.
Peroxisomes are highly dynamic subcellular compartments with important functions in lipid and ROS metabolism. Impaired peroxisomal function can lead to severe metabolic disorders with developmental defects and neurological abnormalities. Recently, a new group of disorders has been identified, characterised by defects in the membrane dynamics and division of peroxisomes rather than by loss of metabolic functions. However, the contribution of impaired peroxisome plasticity to the pathophysiology of those disorders is not well understood. Mitochondrial fission factor (MFF) is a key component of both the peroxisomal and mitochondrial division machinery. Patients with MFF deficiency present with developmental and neurological abnormalities. Peroxisomes (and mitochondria) in patient fibroblasts are highly elongated as a result of impaired organelle division. The majority of studies into MFF-deficiency have focused on mitochondrial dysfunction, but the contribution of peroxisomal alterations to the pathophysiology is largely unknown. Here, we show that MFF deficiency does not cause alterations to overall peroxisomal biochemical function. However, loss of MFF results in reduced import-competency of the peroxisomal compartment and leads to the accumulation of pre-peroxisomal membrane structures. We show that peroxisomes in MFF-deficient cells display alterations in peroxisomal redox state and intra-peroxisomal pH. Removal of elongated peroxisomes through induction of autophagic processes is not impaired. A mathematical model describing key processes involved in peroxisome dynamics sheds further light into the physical processes disturbed in MFF-deficient cells. The consequences of our findings for the pathophysiology of MFF-deficiency and related disorders with impaired peroxisome plasticity are discussed.
Abstract.
Author URL.
Richards DM (2020). Receptor Models of Phagocytosis: the Effect of Target Shape.
Adv Exp Med Biol,
1246, 55-70.
Abstract:
Receptor Models of Phagocytosis: the Effect of Target Shape.
Phagocytosis is a remarkably complex process, requiring simultaneous organisation of the cell membrane, the cytoskeleton, receptors and various signalling molecules. As can often be the case, mathematical modelling is able to penetrate some of this complexity, identifying the key biophysical components and generating understanding that would take far longer with a purely experimental approach. This chapter will review a particularly important class of phagocytosis model, championed in recent years, that primarily focuses on the role of receptors during the engulfment process. These models are pertinent to a host of unsolved questions in the subject, including the rate of cup growth during uptake, the role of both intra- and extracellular noise, and the precise differences between phagocytosis and other forms of endocytosis. In particular, this chapter will focus on the effect of target shape and orientation, including how these influence the rate and final outcome of phagocytic engulfment.
Abstract.
Author URL.
Castro IG, Richards DM, Metz J, Costello JL, Passmore JB, Schrader TA, Gouveia A, Ribeiro D, Schrader M (2018). A role for Mitochondrial Rho GTPase 1 (MIRO1) in motility and membrane dynamics of peroxisomes. Traffic, 19(3), 229-242.
Richards DM, Endres RG (2017). How cells engulf: a review of theoretical approaches to phagocytosis. Reports on Progress in Physics, 80(12), 126601-126601.
Richards DM, Endres RG (2016). Target shape dependence in a simple model of receptor-mediated endocytosis and phagocytosis.
Proceedings of the National Academy of Sciences of the United States of America,
113, 6113-6118.
Abstract:
Target shape dependence in a simple model of receptor-mediated endocytosis and phagocytosis
Phagocytosis and receptor-mediated endocytosis are vitally important particle uptake mechanisms in many cell types, ranging fromsingle-cell organisms to immune cells. In both processes, engulfment by the cell depends critically on both particle shape and orientation. However, most previous theoretical work has focused only on spherical particles and hence disregards the wide-ranging particle shapes occurring in nature, such as those of bacteria. Here, by implementing a simple model in one and two dimensions, we compare and contrast receptormediated endocytosis and phagocytosis for a range of biologically relevant shapes, including spheres, ellipsoids, capped cylinders, and hourglasses. We find awhole range of different engulfment behaviors with some ellipsoids engulfing faster than spheres, and that phagocytosis is able to engulf a greater range of target shapes than other types of endocytosis. Further, the 2D model can explain why some nonspherical particles engulf fastest (not at all) when presented to the membrane tip-first (lying flat). Our work reveals how some bacteria may avoid being internalized simply because of their shape, and suggests shapes for optimal drug delivery.
Abstract.
Micali G, Aquino G, Richards DM, Endres RG (2015). Accurate Encoding and Decoding by Single Cells: Amplitude Versus Frequency Modulation. PLOS Computational Biology, 11(6), e1004222-e1004222.
Richards DM, Saunders TE (2015). Spatiotemporal Analysis of Different Mechanisms for Interpreting Morphogen Gradients. Biophysical Journal, 108(8), 2061-2073.
Richards DM, Endres RG (2014). The Mechanism of Phagocytosis: Two Stages of Engulfment. Biophysical Journal, 107(7), 1542-1553.
Richards D, Berry S, Howard M (2013). Illustrations of Mathematical Modeling in Biology: Epigenetics, Meiosis, and an Outlook. Cold Spring Harbor Symposia on Quantitative Biology, 77(0), 175-181.
Richards DM, Hempel AM, Flärdh K, Buttner MJ, Howard M (2012). Mechanistic basis of branch-site selection in filamentous bacteria.
PLoS Computational Biology,
8(3).
Abstract:
Mechanistic basis of branch-site selection in filamentous bacteria
Many filamentous organisms, such as fungi, grow by tip-extension and by forming new branches behind the tips. A similar growth mode occurs in filamentous bacteria, including the genus Streptomyces, although here our mechanistic understanding has been very limited. The Streptomyces protein DivIVA is a critical determinant of hyphal growth and localizes in foci at hyphal tips and sites of future branch development. However, how such foci form was previously unknown. Here, we show experimentally that DivIVA focus-formation involves a novel mechanism in which new DivIVA foci break off from existing tip-foci, bypassing the need for initial nucleation or de novo branch-site selection. We develop a mathematical model for DivIVA-dependent growth and branching, involving DivIVA focus-formation by tip-focus splitting, focus growth, and the initiation of new branches at a critical focus size. We quantitatively fit our model to the experimentally-measured tip-to-branch and branch-to-branch length distributions. The model predicts a particular bimodal tip-to-branch distribution results from tip-focus splitting, a prediction we confirm experimentally. Our work provides mechanistic understanding of a novel mode of hyphal growth regulation that may be widely employed. © 2012 Richards et al.
Abstract.
Richards DM, Greer E, Martin AC, Moore G, Shaw PJ, Howard M (2012). Quantitative Dynamics of Telomere Bouquet Formation. PLoS Computational Biology, 8(12), e1002812-e1002812.
Flardh K, Richards DM, Hempel AM, Howard M, Buttner MJ (2012). Regulation of apical growth and hyphal branching in Streptomyces.
CURRENT OPINION IN MICROBIOLOGY,
15(6), 737-743.
Author URL.
Hempel AM, Cantlay S, Molle V, Wang S-B, Naldrett MJ, Parker JL, Richards DM, Jung Y-G, Buttner MJ, Flärdh K, et al (2012). The Ser/Thr protein kinase AfsK regulates polar growth and hyphal branching in the filamentous bacteria. <i>Streptomyces</i>.
Proceedings of the National Academy of Sciences,
109(35).
Abstract:
The Ser/Thr protein kinase AfsK regulates polar growth and hyphal branching in the filamentous bacteria. Streptomyces
. In cells that exhibit apical growth, mechanisms that regulate cell polarity are crucial for determination of cellular shape and for the adaptation of growth to intrinsic and extrinsic cues. Broadly conserved pathways control cell polarity in eukaryotes, but less is known about polarly growing prokaryotes. An evolutionarily ancient form of apical growth is found in the filamentous bacteria
. Streptomyces
. and is directed by a polarisome-like complex involving the essential protein DivIVA. We report here that this bacterial polarization machinery is regulated by a eukaryotic-type Ser/Thr protein kinase, AfsK, which localizes to hyphal tips and phosphorylates DivIVA. During normal growth, AfsK regulates hyphal branching by modulating branch-site selection and some aspect of the underlying polarisome-splitting mechanism that controls branching of
. Streptomyces
. hyphae. Further, AfsK is activated by signals generated by the arrest of cell wall synthesis and directly communicates this to the polarisome by hyperphosphorylating DivIVA. Induction of high levels of DivIVA phosphorylation by using a constitutively active mutant AfsK causes disassembly of apical polarisomes, followed by establishment of multiple hyphal branches elsewhere in the cell, revealing a profound impact of this kinase on growth polarity. The function of AfsK is reminiscent of the phoshorylation of polarity proteins and polarisome components by Ser/Thr protein kinases in eukaryotes.
.
Abstract.
Richards DM (2008). The one-loop five-graviton amplitude and the effective action. Journal of High Energy Physics, 2008(10), 042-042.
Richards DM (2008). The one-loop<i>H</i><sup>2</sup><i>R</i><sup>3</sup>and<i>H</i><sup>2</sup>(∇<i>H</i>)<sup>2</sup><i>R</i>terms in the effective action. Journal of High Energy Physics, 2008(10), 043-043.
Publications by year
In Press
Migdalska-Richards A, Smith AR, Richards DM, Schapira AH, Lunnon K (In Press). DNA Methylation of α-Synuclein Intron 1 is Significantly Decreased in the Frontal Cortex of Parkinson’s Individuals with GBA1 Mutations. International Journal of Molecular Sciences
Carmichael R, Richards D, Fahimi HD, Schrader M (In Press). Organelle Membrane Extensions in Mammalian Cells. Biology
Valente F, Mansfield J, Herring D, Romana G, Rodrigues C, Metz J, Craze M, Bowden S, Greenland A, Moger J, et al (In Press). Wheat cells show positional responses to invasive <i>Zymoseptoria tritici</i>.
Abstract:
Wheat cells show positional responses to invasive Zymoseptoria tritici
SummaryThe stomatal complex of grasses consists of two guard cells and two adjacent subsidiary cells that cooperate during stomatal closure. Zymoseptoria tritici, the main causal agent of Septoria tritici blotch in wheat, enters the host via stomata. Here we test the hypothesis that the stomatal complex shows focused sub-cellular responses to invading Z. tritici hyphae.We have combined live-cell transmission light microscopy, immunofluorescence and CRS microscopy to identify cell wall modifications triggered by hyphal invasion. Furthermore, we have used confocal fluorescence microscopy and automated quantitative image analysis to assess whether host cells respond to hyphae through spatial redistribution of organelles.We find that subsidiary cells construct papillae that are accurately aligned with hyphal position even when hyphae are occluded by guard cells. These are distinct from those induced by powdery mildew, with callose restricted to a crust that surrounds content with a high-amplitude Raman signal in the CH-band. Peroxisome populations in subsidiary cells show distributions with modes weakly correlated with hyphal position but do not differ significantly between compatible and incompatible interactions.Our data suggest local changes to cell wall architecture and focal accumulation of organelles in subsidiary cells could play roles in crop defence during host leaf penetration by Z. tritici. Molecular strategies to amplify these responses may provide novel routes for crop protection.
Abstract.
2023
Hembrow J, Deeks MJ, Richards DM (2023). AUTOMATIC EXTRACTION OF ACTIN NETWORKS IN PLANTS.
Hembrow J, Deeks MJ, Richards DM (2023). Automatic extraction of actin networks in plants.
PLOS Computational Biology,
19(8), e1011407-e1011407.
Abstract:
Automatic extraction of actin networks in plants
The actin cytoskeleton is essential in eukaryotes, not least in the plant kingdom where it plays key roles in cell expansion, cell division, environmental responses and pathogen defence. Yet, the precise structure-function relationships of properties of the actin network in plants are still to be unravelled, including details of how the network configuration depends upon cell type, tissue type and developmental stage. Part of the problem lies in the difficulty of extracting high-quality, quantitative measures of actin network features from microscopy data. To address this problem, we have developed DRAGoN, a novel image analysis algorithm that can automatically extract the actin network across a range of cell types, providing seventeen different quantitative measures that describe the network at a local level. Using this algorithm, we then studied a number of cases in Arabidopsis thaliana, including several different tissues, a variety of actin-affected mutants, and cells responding to powdery mildew. In many cases we found statistically-significant differences in actin network properties. In addition to these results, our algorithm is designed to be easily adaptable to other tissues, mutants and plants, and so will be a valuable asset for the study and future biological engineering of the actin cytoskeleton in globally-important crops.
Abstract.
Richards D, Cockerell A, Wright L, Dattani A, Guo G, Smith A, Tsaneva K (2023). Biophysical models of early mammalian embryogenesis. Stem Cell Reports, 18, 26-46.
Giuraniuc C, Parkin C, Almeida M, Fricker M, Shadmani P, Nye S, Wehmeier S, Chawla S, Bedekovic T, Lehtovirta-Morley L, et al (2023). Dynamic calcium-mediated stress response and recovery signatures in the fungal pathogen, Candida albicans.
2020
Richards DM, Walker JJ, Tabak J (2020). Ion channel noise shapes the electrical activity of endocrine cells.
PLoS Comput Biol,
16(4).
Abstract:
Ion channel noise shapes the electrical activity of endocrine cells.
Endocrine cells in the pituitary gland typically display either spiking or bursting electrical activity, which is related to the level of hormone secretion. Recent work, which combines mathematical modelling with dynamic clamp experiments, suggests the difference is due to the presence or absence of a few large-conductance potassium channels. Since endocrine cells only contain a handful of these channels, it is likely that stochastic effects play an important role in the pattern of electrical activity. Here, for the first time, we explicitly determine the effect of such noise by studying a mathematical model that includes the realistic noisy opening and closing of ion channels. This allows us to investigate how noise affects the electrical activity, examine the origin of spiking and bursting, and determine which channel types are responsible for the greatest noise. Further, for the first time, we address the role of cell size in endocrine cell electrical activity, finding that larger cells typically display more bursting, while the smallest cells almost always only exhibit spiking behaviour.
Abstract.
Author URL.
Passmore JB, Carmichael RE, Schrader TA, Godinho LF, Ferdinandusse S, Lismont C, Wang Y, Hacker C, Islinger M, Fransen M, et al (2020). Mitochondrial fission factor (MFF) is a critical regulator of peroxisome maturation.
Biochim Biophys Acta Mol Cell Res,
1867(7).
Abstract:
Mitochondrial fission factor (MFF) is a critical regulator of peroxisome maturation.
Peroxisomes are highly dynamic subcellular compartments with important functions in lipid and ROS metabolism. Impaired peroxisomal function can lead to severe metabolic disorders with developmental defects and neurological abnormalities. Recently, a new group of disorders has been identified, characterised by defects in the membrane dynamics and division of peroxisomes rather than by loss of metabolic functions. However, the contribution of impaired peroxisome plasticity to the pathophysiology of those disorders is not well understood. Mitochondrial fission factor (MFF) is a key component of both the peroxisomal and mitochondrial division machinery. Patients with MFF deficiency present with developmental and neurological abnormalities. Peroxisomes (and mitochondria) in patient fibroblasts are highly elongated as a result of impaired organelle division. The majority of studies into MFF-deficiency have focused on mitochondrial dysfunction, but the contribution of peroxisomal alterations to the pathophysiology is largely unknown. Here, we show that MFF deficiency does not cause alterations to overall peroxisomal biochemical function. However, loss of MFF results in reduced import-competency of the peroxisomal compartment and leads to the accumulation of pre-peroxisomal membrane structures. We show that peroxisomes in MFF-deficient cells display alterations in peroxisomal redox state and intra-peroxisomal pH. Removal of elongated peroxisomes through induction of autophagic processes is not impaired. A mathematical model describing key processes involved in peroxisome dynamics sheds further light into the physical processes disturbed in MFF-deficient cells. The consequences of our findings for the pathophysiology of MFF-deficiency and related disorders with impaired peroxisome plasticity are discussed.
Abstract.
Author URL.
Richards DM (2020). Receptor Models of Phagocytosis: the Effect of Target Shape.
Adv Exp Med Biol,
1246, 55-70.
Abstract:
Receptor Models of Phagocytosis: the Effect of Target Shape.
Phagocytosis is a remarkably complex process, requiring simultaneous organisation of the cell membrane, the cytoskeleton, receptors and various signalling molecules. As can often be the case, mathematical modelling is able to penetrate some of this complexity, identifying the key biophysical components and generating understanding that would take far longer with a purely experimental approach. This chapter will review a particularly important class of phagocytosis model, championed in recent years, that primarily focuses on the role of receptors during the engulfment process. These models are pertinent to a host of unsolved questions in the subject, including the rate of cup growth during uptake, the role of both intra- and extracellular noise, and the precise differences between phagocytosis and other forms of endocytosis. In particular, this chapter will focus on the effect of target shape and orientation, including how these influence the rate and final outcome of phagocytic engulfment.
Abstract.
Author URL.
2018
Castro IG, Richards DM, Metz J, Costello JL, Passmore JB, Schrader TA, Gouveia A, Ribeiro D, Schrader M (2018). A role for Mitochondrial Rho GTPase 1 (MIRO1) in motility and membrane dynamics of peroxisomes. Traffic, 19(3), 229-242.
2017
Richards DM, Endres RG (2017). How cells engulf: a review of theoretical approaches to phagocytosis. Reports on Progress in Physics, 80(12), 126601-126601.
2016
Richards DM, Endres RG (2016). Target shape dependence in a simple model of receptor-mediated endocytosis and phagocytosis.
Proceedings of the National Academy of Sciences of the United States of America,
113, 6113-6118.
Abstract:
Target shape dependence in a simple model of receptor-mediated endocytosis and phagocytosis
Phagocytosis and receptor-mediated endocytosis are vitally important particle uptake mechanisms in many cell types, ranging fromsingle-cell organisms to immune cells. In both processes, engulfment by the cell depends critically on both particle shape and orientation. However, most previous theoretical work has focused only on spherical particles and hence disregards the wide-ranging particle shapes occurring in nature, such as those of bacteria. Here, by implementing a simple model in one and two dimensions, we compare and contrast receptormediated endocytosis and phagocytosis for a range of biologically relevant shapes, including spheres, ellipsoids, capped cylinders, and hourglasses. We find awhole range of different engulfment behaviors with some ellipsoids engulfing faster than spheres, and that phagocytosis is able to engulf a greater range of target shapes than other types of endocytosis. Further, the 2D model can explain why some nonspherical particles engulf fastest (not at all) when presented to the membrane tip-first (lying flat). Our work reveals how some bacteria may avoid being internalized simply because of their shape, and suggests shapes for optimal drug delivery.
Abstract.
2015
Micali G, Aquino G, Richards DM, Endres RG (2015). Accurate Encoding and Decoding by Single Cells: Amplitude Versus Frequency Modulation. PLOS Computational Biology, 11(6), e1004222-e1004222.
Richards DM, Saunders TE (2015). Spatiotemporal Analysis of Different Mechanisms for Interpreting Morphogen Gradients. Biophysical Journal, 108(8), 2061-2073.
2014
Richards DM, Endres RG (2014). The Mechanism of Phagocytosis: Two Stages of Engulfment. Biophysical Journal, 107(7), 1542-1553.
2013
Richards D, Berry S, Howard M (2013). Illustrations of Mathematical Modeling in Biology: Epigenetics, Meiosis, and an Outlook. Cold Spring Harbor Symposia on Quantitative Biology, 77(0), 175-181.
2012
Richards DM, Hempel AM, Flärdh K, Buttner MJ, Howard M (2012). Mechanistic basis of branch-site selection in filamentous bacteria.
PLoS Computational Biology,
8(3).
Abstract:
Mechanistic basis of branch-site selection in filamentous bacteria
Many filamentous organisms, such as fungi, grow by tip-extension and by forming new branches behind the tips. A similar growth mode occurs in filamentous bacteria, including the genus Streptomyces, although here our mechanistic understanding has been very limited. The Streptomyces protein DivIVA is a critical determinant of hyphal growth and localizes in foci at hyphal tips and sites of future branch development. However, how such foci form was previously unknown. Here, we show experimentally that DivIVA focus-formation involves a novel mechanism in which new DivIVA foci break off from existing tip-foci, bypassing the need for initial nucleation or de novo branch-site selection. We develop a mathematical model for DivIVA-dependent growth and branching, involving DivIVA focus-formation by tip-focus splitting, focus growth, and the initiation of new branches at a critical focus size. We quantitatively fit our model to the experimentally-measured tip-to-branch and branch-to-branch length distributions. The model predicts a particular bimodal tip-to-branch distribution results from tip-focus splitting, a prediction we confirm experimentally. Our work provides mechanistic understanding of a novel mode of hyphal growth regulation that may be widely employed. © 2012 Richards et al.
Abstract.
Richards DM, Greer E, Martin AC, Moore G, Shaw PJ, Howard M (2012). Quantitative Dynamics of Telomere Bouquet Formation. PLoS Computational Biology, 8(12), e1002812-e1002812.
Flardh K, Richards DM, Hempel AM, Howard M, Buttner MJ (2012). Regulation of apical growth and hyphal branching in Streptomyces.
CURRENT OPINION IN MICROBIOLOGY,
15(6), 737-743.
Author URL.
Hempel AM, Cantlay S, Molle V, Wang S-B, Naldrett MJ, Parker JL, Richards DM, Jung Y-G, Buttner MJ, Flärdh K, et al (2012). The Ser/Thr protein kinase AfsK regulates polar growth and hyphal branching in the filamentous bacteria. <i>Streptomyces</i>.
Proceedings of the National Academy of Sciences,
109(35).
Abstract:
The Ser/Thr protein kinase AfsK regulates polar growth and hyphal branching in the filamentous bacteria. Streptomyces
. In cells that exhibit apical growth, mechanisms that regulate cell polarity are crucial for determination of cellular shape and for the adaptation of growth to intrinsic and extrinsic cues. Broadly conserved pathways control cell polarity in eukaryotes, but less is known about polarly growing prokaryotes. An evolutionarily ancient form of apical growth is found in the filamentous bacteria
. Streptomyces
. and is directed by a polarisome-like complex involving the essential protein DivIVA. We report here that this bacterial polarization machinery is regulated by a eukaryotic-type Ser/Thr protein kinase, AfsK, which localizes to hyphal tips and phosphorylates DivIVA. During normal growth, AfsK regulates hyphal branching by modulating branch-site selection and some aspect of the underlying polarisome-splitting mechanism that controls branching of
. Streptomyces
. hyphae. Further, AfsK is activated by signals generated by the arrest of cell wall synthesis and directly communicates this to the polarisome by hyperphosphorylating DivIVA. Induction of high levels of DivIVA phosphorylation by using a constitutively active mutant AfsK causes disassembly of apical polarisomes, followed by establishment of multiple hyphal branches elsewhere in the cell, revealing a profound impact of this kinase on growth polarity. The function of AfsK is reminiscent of the phoshorylation of polarity proteins and polarisome components by Ser/Thr protein kinases in eukaryotes.
.
Abstract.
2008
Richards DM (2008). The one-loop five-graviton amplitude and the effective action. Journal of High Energy Physics, 2008(10), 042-042.
Richards DM (2008). The one-loop<i>H</i><sup>2</sup><i>R</i><sup>3</sup>and<i>H</i><sup>2</sup>(∇<i>H</i>)<sup>2</sup><i>R</i>terms in the effective action. Journal of High Energy Physics, 2008(10), 043-043.
