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Singapore, Singapore

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Singapore, Singapore
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Lin H.-H.,University of California at San Diego | Cao D.-S.,University of California at San Diego | Sethi S.,University of California at San Diego | Zeng Z.,University of California at San Diego | And 8 more authors.
Neuron | Year: 2016

During the lifespans of most animals, reproductive maturity and mating activity are highly coordinated. In Drosophila melanogaster, for instance, male fertility increases with age, and older males are known to have a copulation advantage over young ones. The molecular and neural basis of this age-related disparity in mating behavior is unknown. Here, we show that the Or47b odorant receptor is required for the copulation advantage of older males. Notably, the sensitivity of Or47b neurons to a stimulatory pheromone, palmitoleic acid, is low in young males but high in older ones, which accounts for older males' higher courtship intensity. Mechanistically, this age-related sensitization of Or47b neurons requires a reproductive hormone, juvenile hormone, as well as its binding protein Methoprene-tolerant in Or47b neurons. Together, our study identifies a direct neural substrate for juvenile hormone that permits coordination of courtship activity with reproductive maturity to maximize male reproductive fitness. © 2016 Elsevier Inc.


Yam C.,Research Link | Yam C.,National University of Singapore | Gu Y.,Research Link | Oliferenko S.,Research Link | And 2 more authors.
Current Biology | Year: 2013

During cellular proliferation, the mother nucleus divides into two daughters, each carrying a full complement of chromosomes and capable of driving the next cell cycle. Mitotic chromosome segregation must be coordinated with remodeling of other nuclear components, including the nuclear envelope (NE) and the non-membrane-bound nucleolus. Here, we show that in the fission yeast Schizosaccharomyces japonicus, which breaks and reforms the NE during mitosis [1, 2], the evolutionary conserved LEM-domain protein Man1 promotes equal partitioning of the nuclear membrane, nucleolar remodeling, and efficient inheritance of the nuclear pore complexes (NPCs) by the daughter nuclei. Analyses of man1 mutants and results obtained using an artificial chromatin-nuclear pore tether suggest that Man1 may exert its function by linking the NPCs to segregating chromatin. By integrating the partitioning of the nuclear membrane and nucleolar material with chromosome segregation, cells build two nearly identical copies of the original nucleus. © 2013 Elsevier Ltd.


Tao E.,National University of Singapore | Calvert M.,Research Link | Balasubramanian MohanK.,University of Warwick
Current Biology | Year: 2014

Correct positioning of the cell division machinery is key to genome stability. Schizosaccharomyces pombe is an attractive organism to study cytokinesis as it, like higher eukaryotes, divides using a contractile actomyosin ring. In S. pombe, many actomyosin ring components assemble at the medial cortex into node-like structures before coalescing into a ring [1, 2]. Assembly of cytokinetic nodes requires Mid1p, which recruits IQGAP-related Rng2p to the division site, after which other node components accumulate at the division site in a characteristic sequence [3-6]. How cytokinetic nodes assemble, whether the order of assembly of ring components is important, and whether Mid1p solely participates in ring positioning are poorly understood. Here, we show that synthetic targeting of IQGAP-related Rng2p, formin-Cdc12p, and myosin II (Myo2p) restores medial division in mid1 mutants, suggesting that ring proteins need not assemble at the division site in an invariant order. Unlike in wild-type cells, actomyosin rings in cells rewired to divide medially in the absence of Mid1p assemble late in anaphase. Furthermore, the rewiring process affects the ability of the actomyosin ring to track the nucleus upon perturbation of nuclear position. Our work reveals the power of synthetic rewiring studies in deciphering roles performed by multifunctional proteins. © 2014 Elsevier Ltd. All rights reserved.


Ye F.,National University of Singapore | Tan L.,National University of Singapore | Yang Q.,National University of Singapore | Xia Y.,National University of Singapore | And 4 more authors.
Current Biology | Year: 2011

Chromosome biorientation and congression during mitosis require precise control of microtubule dynamics [1-4]. The dynamics of kinetochore microtubules (K-MTs) are regulated by a variety of microtubule-associated proteins (MAPs) [4-9]. Recently, a MAP known as HURP (hepatoma upregulated protein) was identified [10-12]. During mitosis, Ran-guanosine 5′-triphosphate (RanGTP) releases HURP from the importin β inhibitory complex and allows it to localize to the kinetochore fiber (k-fiber) [12, 13]. HURP stabilizes k-fibers and promotes chromosome congression [12, 14, 15]. However, the molecular mechanism underlying the role of HURP in regulating chromosome congression remains elusive. Here, we show that overexpression of the N-terminal microtubule binding domain (1-278 aa, HURP 278) of HURP induces a series of mitotic defects that mimic the effects of Kif18A depletion. In addition, coimmunoprecipitation and bimolecular fluorescence complementation assays identify Kif18A as a novel interaction partner of HURP. Furthermore, quantitative results from live-cell imaging analyses illustrate that HURP regulates Kif18A localization and dynamics at the plus end of K-MTs. Lastly, misaligned chromosomes in HURP 278-overexpressing cells can be partially rescued by the overexpression of Kif18A. Our results demonstrate in part the regulatory mechanism for Kif18A during chromosome congression and provide new insights into the mechanism of chromosome movement at the metaphase plate. © 2011 Elsevier Ltd. All rights reserved.


Zhang D.,Research Link | Zhang D.,National University of Singapore | Vjestica A.,Research Link | Vjestica A.,National University of Singapore | And 2 more authors.
Current Biology | Year: 2012

The cortical endoplasmic reticulum (ER) is an intricate network of tubules and cisternae tightly associated with the plasma membrane (PM) in plants, yeast, and the excitable cell types in metazoans [1-5]. How the ER is attached to the cell cortex and what necessitates its highly reticulated architecture remain largely unknown. Here, we identify the integral ER vesicle-associated membrane protein-associated proteins (VAPs), previously shown to control the composition of phosphoinositides at the ER-PM contact sites [6, 7], as major players in sustaining the ER-PM tethering in fission yeast. We show that genetic conversion of the reticulated ER structure to the cisternal morphology shields large areas of the PM, preventing the actomyosin division ring assembly at the equatorial cortex. Using a combination of VAP mutants where the cortical ER is detached from the PM and a set of artificial ER-PM tethers suppressing this phenotype, we demonstrate that the PM footprint of the cortical ER is functionally insulated from the cytosol. In cells with prominent ER-PM contacts, fine reticulation of the ER network may have emerged as a critical adaptation enabling a uniform access of peripheral protein complexes to the inner surface of the plasma membrane. © 2012 Elsevier Ltd.


Zhang D.,Research Link | Zhang D.,National University of Singapore | Oliferenko S.,Research Link | Oliferenko S.,National University of Singapore
Current Opinion in Cell Biology | Year: 2013

The mitotic spindle assembly and chromosome segregation in eukaryotes must be coordinated with the nuclear envelope (NE) remodeling. In a so-called 'open' mitosis the envelope of the mother nucleus is dismantled allowing the cytoplasmic spindle microtubules to capture the chromosomes. Alternatively, cells undergoing 'closed' mitosis assemble the intranuclear spindle and divide the nucleus without ever losing the nucleocytoplasmic compartmentalization. Here we focus on the mechanisms underlying mitotic NE dynamics in unicellular eukaryotes undergoing a closed nuclear division, paying specific attention to the emerging roles of the lipid biosynthesis machinery in this process. We argue that lessons learned in these organisms may be generally relevant to understanding the NE remodeling and the evolution of mitotic mechanisms throughout the eukaryotic domain. © 2012 Elsevier Ltd.


Zhang D.,Research Link | Zhang D.,National University of Singapore | Vjestica A.,Research Link | Vjestica A.,National University of Singapore | And 2 more authors.
Current Biology | Year: 2010

Precise positioning of the cellular division plane is important for accurate segregation of genetic material and determination of daughter cell fates. Here we report a surprising connection between division site positioning and the organization of the cortical endoplasmic reticulum (ER). The cortical ER is an interconnected network of flat cisternae and highly curved tubules sharing a continuous lumen [1, 2]. Stabilization of high curvature by reticulon and DP1 family proteins contributes to formation of tubules [3-5]. We show that in the fission yeast Schizosaccharomyces pombe, the ER network is maintained by a set of three membrane proteins: reticulon/Rtn1p, DP1/Yop1p, and a newly identified evolutionarily conserved protein, Tts1p. Cells lacking the ER domain sustained by these proteins exhibit severe defects in division plane positioning as a result of abnormal dispersion of a key regulator of division site selection, Mid1p, along the cell cortex. This triggers delocalized assembly of actomyosin cables and compromises their compaction into a single medially positioned ring. We propose that the cortical ER network restricts the lateral motion of Mid1p and hence generates a permissive zone for actomyosin ring assembly precisely at the cell equator. © 2010 Elsevier Ltd. All rights reserved.


Lee Y.H.,National University of Singapore | Chen Y.,National University of Singapore | Ouyang X.,Research Link | Gan Y.-H.,National University of Singapore
BMC Microbiology | Year: 2010

Background. Burkholderia pseudomallei is the causative agent for melioidosis, a disease with significant mortality and morbidity in endemic regions. Its versatility as a pathogen is reflected in its relatively huge 7.24 Mb genome and the presence of many virulence factors including three Type Three Secretion Systems known as T3SS1, T3SS2 and T3SS3. Besides being a human pathogen, it is able to infect and cause disease in many different animals and alternative hosts such as C. elegans. Results. Its host range is further extended to include plants as we demonstrated the ability of B. pseudomallei and the closely related species B. thailandensis to infect susceptible tomato but not rice plants. Bacteria were found to multiply intercellularly and were found in the xylem vessels of the vascular bundle. Disease is substantially attenuated upon infection with bacterial mutants deficient in T3SS1 or T3SS2 and slightly attenuated upon infection with the T3SS3 mutant. This shows the importance of both T3SS1 and T3SS2 in bacterial pathogenesis in susceptible plants. Conclusions. The potential of B. pseudomallei as a plant pathogen raises new possibilities of exploiting plant as an alternative host for novel anti-infectives or virulence factor discovery. It also raises issues of biosecurity due to its classification as a potential bioterrorism agent. © 2010 Lee et al; licensee BioMed Central Ltd.


Zhang D.,Research Link | Bidone T.C.,Lehigh University | Vavylonis D.,Lehigh University
Current Biology | Year: 2016

The cortical endoplasmic reticulum (ER), an elaborate network of tubules and cisternae [1], establishes contact sites with the plasma membrane (PM) through tethering machinery involving a set of conserved integral ER proteins [2]. The physiological consequences of forming ER-PM contacts are not fully understood. Here, we reveal a kinetic restriction role of ER-PM contacts over ring compaction process for proper actomyosin ring assembly in Schizosaccharomyces pombe. We show that fission yeast cells deficient in ER-PM contacts exhibit aberrant equatorial clustering of actin cables during ring assembly and are particularly susceptible to compromised actin filament crosslinking activity. Using quantitative image analyses and computer simulation, we demonstrate that ER-PM contacts function to modulate the distribution of ring components and to constrain their compaction kinetics. We propose that ER-PM contacts have evolved as important physical modulators to ensure robust ring assembly. © 2016 Elsevier Ltd. All rights reserved.


Zhang D.,Research Link
Current opinion in cell biology | Year: 2013

The mitotic spindle assembly and chromosome segregation in eukaryotes must be coordinated with the nuclear envelope (NE) remodeling. In a so-called 'open' mitosis the envelope of the mother nucleus is dismantled allowing the cytoplasmic spindle microtubules to capture the chromosomes. Alternatively, cells undergoing 'closed' mitosis assemble the intranuclear spindle and divide the nucleus without ever losing the nucleocytoplasmic compartmentalization. Here we focus on the mechanisms underlying mitotic NE dynamics in unicellular eukaryotes undergoing a closed nuclear division, paying specific attention to the emerging roles of the lipid biosynthesis machinery in this process. We argue that lessons learned in these organisms may be generally relevant to understanding the NE remodeling and the evolution of mitotic mechanisms throughout the eukaryotic domain. Copyright © 2012 Elsevier Ltd. All rights reserved.

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