Faculty Opinions recommendation of Mechanism of microtubule stabilization by doublecortin.

Author(s):  
Orly Reiner
2020 ◽  
Vol 20 (12) ◽  
pp. 1059-1073 ◽  
Author(s):  
Ahmad Abu Turab Naqvi ◽  
Gulam Mustafa Hasan ◽  
Md. Imtaiyaz Hassan

Microtubule-associated protein tau is involved in the tubulin binding leading to microtubule stabilization in neuronal cells which is essential for stabilization of neuron cytoskeleton. The regulation of tau activity is accommodated by several kinases which phosphorylate tau protein on specific sites. In pathological conditions, abnormal activity of tau kinases such as glycogen synthase kinase-3 β (GSK3β), cyclin-dependent kinase 5 (CDK5), c-Jun N-terminal kinases (JNKs), extracellular signal-regulated kinase 1 and 2 (ERK1/2) and microtubule affinity regulating kinase (MARK) lead to tau hyperphosphorylation. Hyperphosphorylation of tau protein leads to aggregation of tau into paired helical filaments like structures which are major constituents of neurofibrillary tangles, a hallmark of Alzheimer’s disease. In this review, we discuss various tau protein kinases and their association with tau hyperphosphorylation. We also discuss various strategies and the advancements made in the area of Alzheimer's disease drug development by designing effective and specific inhibitors for such kinases using traditional in vitro/in vivo methods and state of the art in silico techniques.


2020 ◽  
Vol 861 ◽  
pp. 303-308
Author(s):  
Guo Li Gong ◽  
Zhi Qiang Liu

Sorangium cellulosum can product many secondary metabolites that is unique structural and makes these microorganisms highly attractive for drug development, especially epothilone, on cancer cells a cytotoxic macrolide which is naturally produced by Soxhlet cellulose that have the action of microtubule stabilization, is a promising anticancer drug. In this research, the factors affecting the regeneration and preparation of the protoplast of Sorangium cellulosum were discussed, those were regeneration media, enzymes and osmotic stabilizers. This study provide the distruction for improving the production of epothilone through genome shuffling, mutation, fusion and transformation.


2015 ◽  
Vol 26 (20) ◽  
pp. 3628-3640 ◽  
Author(s):  
Christine M. Field ◽  
Aaron C. Groen ◽  
Phuong A. Nguyen ◽  
Timothy J. Mitchison

Mitotic spindles specify cleavage planes in early embryos by communicating their position and orientation to the cell cortex using microtubule asters that grow out from the spindle poles during anaphase. Chromatin also plays a poorly understood role. Polyspermic fertilization provides a natural experiment in which aster pairs from the same spindle (sister asters) have chromatin between them, whereas asters pairs from different spindles (nonsisters) do not. In frogs, only sister aster pairs induce furrows. We found that only sister asters recruited two conserved furrow-inducing signaling complexes, chromosome passenger complex (CPC) and Centralspindlin, to a plane between them. This explains why only sister pairs induce furrows. We then investigated factors that influenced CPC recruitment to microtubule bundles in intact eggs and a cytokinesis extract system. We found that microtubule stabilization, optimal starting distance between asters, and proximity to chromatin all favored CPC recruitment. We propose a model in which proximity to chromatin biases initial CPC recruitment to microtubule bundles between asters from the same spindle. Next a positive feedback between CPC recruitment and microtubule stabilization promotes lateral growth of a plane of CPC-positive microtubule bundles out to the cortex to position the furrow.


2011 ◽  
Vol 439 (1) ◽  
pp. 79-83 ◽  
Author(s):  
Girish K. Radhakrishnan ◽  
Jerome S. Harms ◽  
Gary A. Splitter

TIR (Toll/interleukin-1 receptor) domain-containing proteins play a crucial role in innate immunity in eukaryotes. Brucella is a highly infectious intracellular bacterium that encodes a TIR domain protein (TcpB) to subvert host innate immune responses to establish a beneficial niche for pathogenesis. TcpB inhibits NF-κB (nuclear factor κB) activation and pro-inflammatory cytokine secretions mediated by TLR (Toll-like receptor) 2 and TLR4. In the present study, we have demonstrated that TcpB modulates microtubule dynamics by acting as a stabilization factor. TcpB increased the rate of nucleation as well as the polymerization phases of microtubule formation in a similar manner to paclitaxel. TcpB could efficiently inhibit nocodazole- or cold-induced microtubule disassembly. Microtubule stabilization by TcpB is attributed to the BB-loop region of the TIR domain, and a point mutation affected the microtubule stabilization as well as the TLR-suppression properties of TcpB.


2008 ◽  
Vol 477 (2) ◽  
pp. 267-278 ◽  
Author(s):  
Tomonari Tsutsumi ◽  
Takamitsu Kosaka ◽  
Hiroshi Ushiro ◽  
Kazushi Kimura ◽  
Tomoyuki Honda ◽  
...  

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