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1.
Hermann Cuntz Friedrich Forstner Bettina Schnell Georg Ammer Shamprasad Varija Raghu Alexander Borst 《PloS one》2013,8(8)
Important brain functions need to be conserved throughout organisms of extremely varying sizes. Here we study the scaling properties of an essential component of computation in the brain: the single neuron. We compare morphology and signal propagation of a uniquely identifiable interneuron, the HS cell, in the blowfly (Calliphora) with its exact counterpart in the fruit fly (Drosophila) which is about four times smaller in each dimension. Anatomical features of the HS cell scale isometrically and minimise wiring costs but, by themselves, do not scale to preserve the electrotonic behaviour. However, the membrane properties are set to conserve dendritic as well as axonal delays and attenuation as well as dendritic integration of visual information. In conclusion, the electrotonic structure of a neuron, the HS cell in this case, is surprisingly stable over a wide range of morphological scales. 相似文献
2.
Paithankar Jagdish Gopal Raghu Shamprasad Varija Patil Rajashekhar K 《Molecular biology reports》2018,45(5):1175-1186
Molecular Biology Reports - Ionizing radiation (IR) causes biological effects either by directly damaging the molecules or by generating free radicals. Antioxidant mechanisms are believed to be... 相似文献
3.
The visual system of Drosophila contains approximately 60,000 neurons that are organized in parallel, retinotopically arranged columns. A large number of these neurons have been characterized in great anatomical detail. However, studies providing direct evidence for synaptic signaling and the neurotransmitter used by individual neurons are relatively sparse. Here we present a first layout of neurons in the Drosophila visual system that likely release glutamate as their major neurotransmitter. We identified 33 different types of neurons of the lamina, medulla, lobula and lobula plate. Based on the previous Golgi-staining analysis, the identified neurons are further classified into 16 major subgroups representing lamina monopolar (L), transmedullary (Tm), transmedullary Y (TmY), Y, medulla intrinsic (Mi, Mt, Pm, Dm, Mi Am), bushy T (T), translobula plate (Tlp), lobula intrinsic (Lcn, Lt, Li), lobula plate tangential (LPTCs) and lobula plate intrinsic (LPi) cell types. In addition, we found 11 cell types that were not described by the previous Golgi analysis. This classification of candidate glutamatergic neurons fosters the future neurogenetic dissection of information processing in circuits of the fly visual system. 相似文献
4.
Xi-Ning?Zhu Dong Hyun?Kim Horng-Ru?Lin Varija?N?Budhavarapu Herbert?B?Rosenbaum Paul?R?Mueller P Renee?YewEmail author 《Cell division》2013,8(1):5
Background
Cell division is positively regulated by cyclin-dependent kinases (CDKs) partnered with cyclins and negatively regulated by CDK inhibitors. In the frog, Xenopus laevis, three types of CDK inhibitors have been described: p27Xic1 (Xic1) which shares sequence homology with both p21Cip1 and p27Kip1 from mammals, p16Xic2 (Xic2) which shares sequence homology with p21Cip1, and p17Xic3 (Xic3) which shares sequence homology with p27Kip1. While past studies have demonstrated that during DNA polymerase switching, Xic1 is targeted for protein turnover dependent upon DNA, Proliferating Cell Nuclear Antigen (PCNA), and the ubiquitin ligase CRL4Cdt2, little is known about the processes that regulate Xic2 or Xic3.Methods
We used the Xenopus interphase egg extract as a model system to examine the regulation of Xic2 by proteolysis and phosphorylation.Results
Our studies indicated that following primer synthesis during the initiation of DNA replication, Xic2 is targeted for DNA- and PCNA-dependent ubiquitin-mediated proteolysis and that Cdt2 can promote Xic2 turnover. Additionally, during interphase, Xic2 is phosphorylated by CDK2 at Ser-98 and Ser-131 in a DNA-independent manner, inhibiting Xic2 turnover. In the presence of double-stranded DNA ends, Xic2 is also phosphorylated at Ser-78 and Ser-81 by a caffeine-sensitive kinase, but this phosphorylation does not alter Xic2 turnover. Conversely, in the presence or absence of DNA, Xic3 was stable in the Xenopus interphase egg extract and did not exhibit a shift indicative of phosphorylation.Conclusions
During interphase, Xic2 is targeted for DNA- and PCNA-dependent proteolysis that is negatively regulated by CDK2 phosphorylation. During a response to DNA damage, Xic2 may be alternatively regulated by phosphorylation by a caffeine-sensitive kinase. Our studies suggest that the three types of Xenopus CDK inhibitors, Xic1, Xic2, and Xic3 appear to be uniquely regulated which may reflect their specialized roles during cell division or early development in the frog.5.
6.
Schnell B Raghu SV Nern A Borst A 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2012,198(5):389-395
Wide-field motion-sensitive neurons in the lobula plate (lobula plate tangential cells, LPTCs) of the fly have been studied
for decades. However, it has never been conclusively shown which cells constitute their major presynaptic elements. LPTCs
are supposed to be rendered directionally selective by integrating excitatory as well as inhibitory input from many local
motion detectors. Based on their stratification in the different layers of the lobula plate, the columnar cells T4 and T5
are likely candidates to provide some of this input. To study their role in motion detection, we performed whole-cell recordings
from LPTCs in Drosophila with T4 and T5 cells blocked using two different genetically encoded tools. In these flies, motion responses were abolished,
while flicker responses largely remained. We thus demonstrate that T4 and T5 cells indeed represent those columnar cells that
provide directionally selective motion information to LPTCs. Contrary to previous assumptions, flicker responses seem to be
largely mediated by a third, independent pathway. This work thus represents a further step towards elucidating the complete
motion detection circuitry of the fly. 相似文献
7.
The lobula plate (LP), which is the third order optic neuropil of flies, houses wide-field neurons which are exquisitely sensitive
to motion. Among Diptera, motion-sensitive neurons of larger flies have been studied at the anatomical and physiological levels.
However, the neurons ofDrosophila lobula plate are relatively less explored. AsDrosophila permits a genetic analysis of neural functions, we have analysed the organization of lobula plate ofDrosophila melanogaster.
Neurons belonging to eight anatomical classes have been observed in the present study. Three neurons of the horizontal system
(HS) have been visualized. The HS north (HSN) neuron, occupying the dorsal lobula plate is stunted in its geometry compared
to that of larger flies. Associated with the HS neurons, thinner horizontal elements known as h-cells have also been visualized
in the present study. Five of the six known neurons of the vertical system (VS) have been visualized. Three additional neurons
in the proximal LP comparable in anatomy to VS system have been stained. We have termed them as additional VS AVS)-like neurons.
Three thinner tangential cells that are comparable to VS neurons, which are elements of twin vertical system (tvs); and two
cells with wide dendritic fields comparable to CH neurons of Diptera have been also observed. Neurons comparable to VS cells
but with ‘tufted’ dendrites have been stained. The HSN and VS1-VS2 neurons are dorsally stunted. This is possibly due to the
shape of the compound eye ofDrosophila which is reduced in the fronto-dorsal region as compared to larger flies 相似文献
8.
Dong Hyun Kim Varija N. Budhavarapu Carlos R. Herrera Hyung Wook Nam Yu Sam Kim P. Renee Yew 《Molecular and cellular biology》2010,30(17):4120-4133
During DNA polymerase switching, the Xenopus laevis Cip/Kip-type cyclin-dependent kinase inhibitor Xic1 associates with trimeric proliferating cell nuclear antigen (PCNA) and is recruited to chromatin, where it is ubiquitinated and degraded. In this study, we show that the predominant E3 for Xic1 in the egg is the Cul4-DDB1-XCdt2 (Xenopus Cdt2) (CRL4Cdt2) ubiquitin ligase. The addition of full-length XCdt2 to the Xenopus extract promotes Xic1 turnover, while the N-terminal domain of XCdt2 (residues 1 to 400) cannot promote Xic1 turnover, despite its ability to bind both Xic1 and DDB1. Further analysis demonstrated that XCdt2 binds directly to PCNA through its C-terminal domain (residues 401 to 710), indicating that this interaction is important for promoting Xic1 turnover. We also identify the cis-acting sequences required for Xic1 binding to Cdt2. Xic1 binds to Cdt2 through two domains (residues 161 to 170 and 179 to 190) directly flanking the Xic1 PCNA binding domain (PIP box) but does not require PIP box sequences (residues 171 to 178). Similarly, human p21 binds to human Cdt2 through residues 156 to 161, adjacent to the p21 PIP box. In addition, we identify five lysine residues (K180, K182, K183, K188, and K193) immediately downstream of the Xic1 PIP box and within the second Cdt2 binding domain as critical sites for Xic1 ubiquitination. Our studies suggest a model in which both the CRL4Cdt2 E3- and PIP box-containing substrates, like Xic1, are recruited to chromatin through independent direct associations with PCNA.The eukaryotic cell cycle is positively regulated by cyclin-dependent kinases (CDKs) and negatively regulated by CDK inhibitors (CKIs) (22, 25, 27, 28). A complete knockout of all CDK inhibitor function, although as yet not attained in mammalian cells, has been accomplished in Saccharomyces cerevisiae and is shown to result in genomic instability due to premature entry into S phase (19). Conversely, the overexpression of cyclin E in mammalian cells has also been observed to induce chromosome instability (31). These studies suggest that CDK inhibitor function can play a critical role in maintaining genomic stability through the proper regulation of DNA replication initiation. Mammalian Cip/Kip-type CDK inhibitors p27 and p21 are stoichiometric inhibitors of CDK2-cyclins that regulate the entry into S phase and are targeted by ubiquitin- and proteasome-dependent proteolysis during the G1-to-S-phase transition (4, 5, 33, 35). In the frog, Xenopus laevis, three types of CDK inhibitors have been identified that share sequence and functional similarities with mammalian p27 and p21. The first type of CDK inhibitor includes the Xenopus inhibitor of CDK (p27Xic1 or Xic1) and kinase inhibitor from Xenopus (p28Kix1 or Kix1), which share ∼90% amino acid sequence identity with each other, preferentially inhibit the activity of CDK2-cyclin E or A and bind all CDK-cyclins and proliferating cell nuclear antigen (PCNAs) (30, 32). The second and third types of Xenopus CDK inhibitors are p16Xic2 and p17Xic3, which share sequence homology with p21 and p27, respectively, and exhibit restricted developmental expression but have not been extensively characterized biochemically (9).In an effort to study the molecular mechanism of Cip/Kip-type CDK inhibitor proteolysis in the context of the temporal events of DNA replication initiation, we utilize the biochemically tractable Xenopus egg extract system. This extract can recapitulate all of the events of semiconservative DNA replication and fully support protein ubiquitination and degradation in the context of DNA replication initiation (3, 36). Using this system, we have shown that during DNA polymerase switching, Xic1 is recruited to sites of DNA replication initiation through its association with proliferating cell nuclear antigen (PCNA) and is targeted for ubiquitination and degradation (6). Using a strategy of PCNA reconstitution to PCNA-depleted extracts, our studies showed that Xic1 ubiquitination and turnover required not only PCNA binding but also the ability of PCNA to be loaded at a site of DNA replication initiation by replication factor C (RFC) (6). Our previous study indicated that like mammalian p27 and p21, Xic1 could be ubiquitinated in vitro by SCFXSkp2 (21), but our subsequent studies suggested that Xenopus Skp2 (XSkp2) levels were very low in the early embryo, and XSkp2 immunodepletion did not stabilize Xic1 in the Xenopus egg extract (our unpublished observations). Therefore, we postulated that in the interphase egg extract, Xic1 was targeted for ubiquitination by an alternate ubiquitin ligase.In this study, we identify Cul4-DDB1-XCdt2 (CRL4Cdt2) as the ubiquitin ligase for Xic1 in the egg. We also identify both the critical residues of Xic1 required for association to Cdt2 and the critical lysine residues of Xic1 ubiquitinated by CRL4Cdt2. Importantly, we report a direct interaction between the C-terminal domain of Cdt2 and PCNA and show that the C-terminal domain of Cdt2 is required to promote the proteolysis of Xic1. Our studies suggest a model for Xic1 ubiquitination and proteolysis which requires the Xic1 PIP box for association with PCNA and Xic1 chromatin recruitment, the Xic1 sequences flanking the PIP box for association with Cdt2, specific lysine residues within the Cdt2 binding domain of Xic1 for efficient Xic1 ubiquitination, and a direct association between the Cdt2 C terminus and PCNA. 相似文献
9.
10.
The antennal lobe was examined by Golgi-silver impregnation to differentiate the glomeruli depending on the source and types
of inputs. Thirty-five of the 43 ‘identified’ olfactory glomeruli were Golgi-silver impregnated in the present study. Seven
glomeruli compared to three, reported previously, were found to be targets of maxillary palp chemosensory neurons. These include
glomeruli VA3, VC2, VM5, VA7m/VA7l of the ventral antennal lobe and DC2, DC3, DM5 of the dorsal antennal lobe. The number
of glomeruli receiving the maxillary palp sensory projections tallies with the number ofDrosophila olfactory receptors (seven) reported to be expressed exclusively in the maxillary palp. Twenty-eight Golgi-impregnated glomeruli
were found to receive input from the antennal nerve. The ratio of glomeruli serving the maxillary palp to those serving the
antenna (∼1:5) matches with the ratio ofDrosophila olfactory receptors expressed in these two olfactory organs respectively. In addition to glomerulus V, glomeruli VP1-3, VL1,
VL2a/2p and VC3m/3l were found to receive ipsilateral projections. Thus, additional ipsilateral glomeruli have been identified. 相似文献