scholarly journals XMAP215 promotes microtubule catastrophe by disrupting the growing microtubule end

2021 ◽  
Vol 220 (10) ◽  
Author(s):  
Veronica Farmer ◽  
Göker Arpağ ◽  
Sarah L. Hall ◽  
Marija Zanic

The GTP-tubulin cap is widely accepted to protect microtubules against catastrophe. The GTP-cap size is thought to increase with the microtubule growth rate, presumably endowing fast-growing microtubules with enhanced stability. It is unknown what GTP-cap properties permit frequent microtubule catastrophe despite fast growth. Here, we investigate microtubules growing in the presence and absence of the polymerase XMAP215. Using EB1 as a GTP-cap marker, we find that GTP-cap size increases regardless of whether growth acceleration is achieved by increasing tubulin concentration or by XMAP215. Despite increased mean GTP-cap size, microtubules grown with XMAP215 display increased catastrophe frequency, in contrast to microtubules grown with more tubulin, for which catastrophe is abolished. However, microtubules polymerized with XMAP215 have large fluctuations in growth rate; display tapered and curled ends; and undergo catastrophe at faster growth rates and with higher EB1 end-localization. Our results suggest that structural perturbations induced by XMAP215 override the protective effects of the GTP-cap, ultimately driving microtubule catastrophe.

2020 ◽  
Author(s):  
Veronica Farmer ◽  
Göker Arpağ ◽  
Sarah Hall ◽  
Marija Zanic

ABSTRACTThe GTP-tubulin cap is widely accepted to protect microtubules against catastrophe. The GTP-cap size is thought to increase with the microtubule growth rate, presumably endowing fast-growing microtubules with enhanced stability. It is unknown what GTP-cap properties permit frequent microtubule catastrophe despite fast growth. Here, we investigate microtubules grown in vitro in the presence and absence of the microtubule polymerase XMAP215. Using EB1 as a GTP-cap marker, we find that GTP-cap size increases regardless of whether growth acceleration is achieved by increasing tubulin concentration or by XMAP215. In spite of the increased mean GTP-cap size, microtubules grown with XMAP215 display increased catastrophe frequency, in contrast to microtubules grown with more tubulin, for which catastrophe is abolished. However, microtubules polymerized with XMAP215 have large fluctuations in growth rate and EB1 intensity; display tapered and curled ends; and undergo catastrophe at faster growth rates and with higher EB1 end-localization. Our results underscore the role of growth irregularities in overall microtubule stability.


2002 ◽  
Vol 67 (3) ◽  
pp. 897-909
Author(s):  
David M. Evans ◽  
M. E. Pantano

Various results have been proved about growth rates of certain sequences of integers associated with infinite permutation groups. Most of these concern the number of orbits of the automorphism group of an ℵ0-categorical structure on the set of unordered n-subsets or on the set of n-tuples of elements of . (Recall that by the Ryll-Nardzewski Theorem, if is countable and ℵ0-categorical, the number of the orbits of its automorphism group Aut() on the set of n-tuples from is finite and equals the number of complete n-types consistent with the theory of .) The book [Ca90] is a convenient reference for these results. One of the oldest (in the realms of ‘folklore’) is that for any sequence (Kn)n∈ℕ of natural numbers there is a countable ℵ0-categorical structure such that the number of orbits of Aut() on the set of n-tuples from is greater than kn for all n.These investigations suggested the study of the growth rate of another sequence. Let be an ℵ0-categorical structure and X be a finite subset of . Let acl(X) be the algebraic closure of X, that is, the union of the finite X-definable subsets of . Equivalently, this is the union of the finite orbits on of Aut()(X), the pointwise stabiliser of X in Aut(). Define


1989 ◽  
Vol 35 (5) ◽  
pp. 578-582 ◽  
Author(s):  
James L. Sinclair ◽  
Martin Alexander

The survival of six bacterial species that had different growth rates was tested in raw sewage and sewage that was rendered free of protozoa. When test bacteria were added to protozoa-free sewage at densities of approximately 105 to 106 cells/mL, five of the six species did not decline below 105 cells/mL. If protozoa were present, the population sizes of all test species were markedly reduced, but bacterial species able to grow faster in artificial media had the larger number of survivors. When the same bacteria were inoculated into protozoa-free sewage at densities of less than 103 cells/mL, only the three species able to grow quickly in artificial media increased in abundance. When the six species were inoculated at the same densities into sewage containing protozoa, the three slow-growing species were rapidly eliminated, and two of the three fast-growing species survived in detectable numbers. We suggest that in environments with intense protozoan predation, protozoa may alter the composition of the bacterial community by eliminating slow-growing bacteria.Key words: growth rate, predation, protozoa, sewage.


2017 ◽  
Vol 60 (4) ◽  
pp. 427-437 ◽  
Author(s):  
Philipp C. Muth ◽  
Anne Valle Zárate

Abstract. The effects of the increase of body weight of contemporary broilers during growth on functional meat quality and color characteristics of the chicken breast muscle are controversially debated. Therefore, male chickens (n = 264) of a fast-growing commercial broiler (Ross 308) and two slow-growing experimental meat-type chicken lines were compared at equal age and at similar body weight in order to investigate the effect of growth rate on selected functional breast meat traits and meat color. Additionally, the breast meat characteristics of birds with different growth profiles were compared within lines. When the body weight of commercial broilers reached about 40 to 60 % of their growth potential, they exhibited particularly high ultimate pH values compared with slow-growing lines. The ability of the meat of fast-growing broilers to retain water during cooking was impaired (5 to 16 percentage points increased cooking loss compared to slow-growing lines), which, in contrast to pH, was only marginally affected by body weight and/or age at slaughter. No unfavorable correlations of breast meat quality traits with the growth profile, represented by growth curve parameters derived from the Gompertz–Laird equation, were detected within any of the investigated chicken lines. It is noteworthy that the associations of ultimate pH and cooking loss with maximum growth speed indicate a non-linear relationship. Thus, some of the functional characteristics of breast meat of the fast-growing broiler resembled the white-striping defect described for poultry meat, but the hypothesis that selection on increased growth rates is detrimental for meat quality per se could not be confirmed. In fact, an elevated growth potential in particular, i.e., body weight at maturity, could have some beneficial effects for the water-holding capacity of breast meat, regardless of the genotypic growth rate.


mBio ◽  
2016 ◽  
Vol 7 (4) ◽  
Author(s):  
Jilong Wang ◽  
Dalai Yan ◽  
Ray Dixon ◽  
Yi-Ping Wang

ABSTRACT A fundamental question in microbial physiology concerns why organisms prefer certain nutrients to others. For example, among different nitrogen sources, ammonium is the preferred nitrogen source, supporting fast growth, whereas alternative nitrogen sources, such as certain amino acids, are considered to be poor nitrogen sources, supporting much slower exponential growth. However, the physiological/regulatory logic behind such nitrogen dietary choices remains elusive. In this study, by engineering Escherichia coli , we switched the dietary preferences toward amino acids, with growth rates equivalent to that of the wild-type strain grown on ammonia. However, when the engineered strain was cultured together with wild-type E. coli , this growth advantage was diminished as a consequence of ammonium leakage from the transport-and-catabolism (TC)-enhanced (TCE) cells, which are preferentially utilized by wild-type bacteria. Our results reveal that the nitrogen regulatory (Ntr) system fine tunes the expression of amino acid transport and catabolism components to match the flux through the ammonia assimilation pathway such that essential nutrients are retained, but, as a consequence, the fast growth rate on amino acids is sacrificed. IMPORTANCE Bacteria exhibit different growth rates under various nutrient conditions. These environmentally related behaviors reflect the coordination between metabolism and the underlying regulatory networks. In the present study, we investigated the intertwined nitrogen metabolic and nitrogen regulatory systems to understand the growth differences between rich and poor nitrogen sources. Although maximal growth rate is considered to be evolutionarily advantageous for bacteria (as remarked by François Jacob, who said that the “dream” of every cell is to become two cells), we showed that negative-feedback loops in the regulatory system inhibit growth rates on amino acids. We demonstrated that in the absence of regulatory feedback, amino acids are capable of supporting fast growth rates, but this results in ammonia leaking out from cells as “waste,” benefiting the growth of competitors. These findings provide important insights into the regulatory logic that controls metabolic flux and ensures nutrient containment but consequently sacrifices growth rate.


2017 ◽  
Author(s):  
Meike T. Wortel ◽  
Elad Noor ◽  
Michael Ferris ◽  
Frank J. Bruggeman ◽  
Wolfram Liebermeister

AbstractMicrobes may maximize the number of daughter cells per time or per amount of nutrients consumed. These two strategies correspond, respectively, to the use of enzyme-efficient or substrate-efficient metabolic pathways. In reality, fast growth is often associated with wasteful, yield-inefficient metabolism, and a general thermodynamic trade-off between growth rate and biomass yield has been proposed to explain this. We studied growth rate/yield trade-offs by using a novel modeling framework, Enzyme-Flux Cost Minimization (EFCM) and by assuming that the growth rate depends directly on the enzyme investment per rate of biomass production. In a comprehensive mathematical model of core metabolism inE. coli, we screened all elementary flux modes leading to cell synthesis, characterized them by the growth rates and yields they provide, and studied the shape of the resulting rate/yield Pareto front. By varying the model parameters, we found that the rate/yield trade-off is not universal, but depends on metabolic kinetics and environmental conditions. A prominent trade-off emerges under oxygen-limited growth, where yield-inefficient pathways support a 2-to-3 times higher growth rate than yield-efficient pathways. EFCM can be widely used to predict optimal metabolic states and growth rates under varying nutrient levels, perturbations of enzyme parameters, and single or multiple gene knockouts.Author SummaryWhen cells compete for nutrients, those that grow faster and produce more offspring per time are favored by natural selection. In contrast, when cells need to maximize the cell number at a limited nutrient supply, fast growth does not matter and an efficient use of nutrients (i.e. high biomass yield) is essential. This raises a basic question about metabolism: can cells achieve high growth rates and yields simultaneously, or is there a conflict between the two goals? Using a new modeling method called Enzymatic Flux Cost Minimization (EFCM), we predict cellular growth rates and find that growth rate/yield trade-offs and the ensuing preference for enzyme-efficient or substrate-efficient metabolic pathways are not universal, but depend on growth conditions such as external glucose and oxygen concentrations.


2020 ◽  
Vol 90 (5) ◽  
pp. 485-492
Author(s):  
Snježana Kužir ◽  
◽  
Krešimir Drašner ◽  
Krešimir Matanović ◽  
Lucija Bastiančić ◽  
...  

The relationship between growth rate and ossification is not consistent among fish. In some species, fast-growing individuals ossify earlier, while in other species, a trade-off between growth rate and ossification exists. This research was conducted to test the hypothesis about the existence of a trade-off mechanism in common carp offspring. For this purpose, specimens from two groups of common carp offspring (96 in total) with different growth rates were sampled at multiple time points between 5 and 29 days post-hatching. The standard length was measured and presented in correlation with the days post-hatching. To evaluate the skeletal system development, whole specimens were fixed in 10% neutral buffered formalin and stained for bone and cartilage. Particular emphasis was placed on the onset of ossification in the clearly visible bones of the head, vertebral column, and fins. According to our findings, larger, fast-growing specimens ossify earlier. The hypothesis on the existence of a trade-off between fast growth and the onset of ossification in common carp was not confirmed in our study.


2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 46-47
Author(s):  
Emily D Schunke ◽  
Jessica E Lowell ◽  
Chad A Stahl ◽  
Bailey N Harsh ◽  
Anna C Dilger

Abstract The pork industry has observed an upward trend in ending live weights, resulting in heavier hot carcass weights (HCW). Heavier HCW positively affects loin tenderness; however, the mechanism of this effect is unclear. One possibility is increased growth rate, associated with greater HCW, resulting in more tender loins. The objective was to determine the effect of growth rate on early and aged pork quality. Pigs (N=634) were divided into three groups based on average daily gain (kg/d) from 12-26wk of age; slow (< 0.96kg/d, n=96), intermediate (0.96-1.16kg/d, n=452), and fast (≥ 1.17kg/d, n=86). The MIXED procedure of SAS was used to evaluate the main effects of growth rate, breed, sex, and their interactions on loin quality. Birth and weaning weight did not differ between growth rate (P≥0.15) but, overall ADG was increased (P<0.001) in fast growing pigs by 0.15 kg/d. Fast and intermediate growing pigs had darker loins (P=0.03) by 0.23 units. Intermediate growing pigs had firmer loins (P=0.04) by 0.07 units. Ventral a* increased as growth rate increased (P=0.04) indicating fast growing pigs had the reddest loins (9.77 vs. 9.26 vs. 8.99). Aged ventral marbling, ultimate pH, purge loss, cook loss, instrumental tenderness, and chop moisture and extractable lipid did not differ (P≥0.32) between growth rate groups. Duroc-sired pigs had increased tenth rib back fat amongst all growth rate groups, but the magnitude of difference was much greater in the slow and intermediate groups. Between all growth rate groups, slow growing Pietrain-sired Pigs had the smallest loineye areas (LEA). Carcass yield, bone-in carcass cutting yield, and boneless carcass cutting yield did not differ (P≥0.37) between growth rate groups. While fast growth rates improved aged ventral visual color, instrumental tenderness did not differ between growth rate groups.


mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Llorenç Fernández-Coll ◽  
Monika Maciag-Dorszynska ◽  
Krishma Tailor ◽  
Stephen Vadia ◽  
Petra Anne Levin ◽  
...  

ABSTRACT The initiation of Escherichia coli chromosomal DNA replication starts with the oligomerization of the DnaA protein at repeat sequences within the origin (ori) region. The amount of ori DNA per cell directly correlates with the growth rate. During fast growth, the cell generation time is shorter than the time required for complete DNA replication; therefore, overlapping rounds of chromosome replication are required. Under these circumstances, the ori region DNA abundance exceeds the DNA abundance in the termination (ter) region. Here, high ori/ter ratios are found to persist in (p)ppGpp-deficient [(p)ppGpp0] cells over a wide range of balanced exponential growth rates determined by medium composition. Evidently, (p)ppGpp is necessary to maintain the usual correlation of slow DNA replication initiation with a low growth rate. Conversely, ori/ter ratios are lowered when cell growth is slowed by incrementally increasing even low constitutive basal levels of (p)ppGpp without stress, as if (p)ppGpp alone is sufficient for this response. There are several previous reports of (p)ppGpp inhibition of chromosomal DNA synthesis initiation that occurs with very high levels of (p)ppGpp that stop growth, as during the stringent starvation response or during serine hydroxamate treatment. This work suggests that low physiological levels of (p)ppGpp have significant functions in growing cells without stress through a mechanism involving negative supercoiling, which is likely mediated by (p)ppGpp regulation of DNA gyrase. IMPORTANCE Bacterial cells regulate their own chromosomal DNA synthesis and cell division depending on the growth conditions, producing more DNA when growing in nutritionally rich media than in poor media (i.e., human gut versus water reservoir). The accumulation of the nucleotide analog (p)ppGpp is usually viewed as serving to warn cells of impending peril due to otherwise lethal sources of stress, which stops growth and inhibits DNA, RNA, and protein synthesis. This work importantly finds that small physiological changes in (p)ppGpp basal levels associated with slow balanced exponential growth incrementally inhibit the intricate process of initiation of chromosomal DNA synthesis. Without (p)ppGpp, initiations mimic the high rates present during fast growth. Here, we report that the effect of (p)ppGpp may be due to the regulation of the expression of gyrase, an important enzyme for the replication of DNA that is a current target of several antibiotics.


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