Drosophila anion exchanger 2 is required for proper ovary development and oogenesis

Benitez, Marimar; Tatapudy, Sumitra; Liu, Yi; Barber, Diane L.; Nystul, Todd

doi:10.1016/j.ydbio.2019.04.018

Cited by 11 publications

(23 citation statements)

References 41 publications

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“…Additionally, pHi dynamics regulates cell-substrate adhesion remodeling and migration, with increased pHi enabling both behaviors (4)(5)(6)(7). Emerging evidence also indicates a critical role for increased pHi in epithelial plasticity, including epithelial to mesenchymal transition (EMT) (8), and stem cell differentiation (9)(10)(11)(12). Moreover, it is now well-established that dysregulated pHi is seen with many diseases, most notably cancers, which often have a constitutively increased pHi (13)(14)(15)(16)(17)(18), and neurodegenerative disorders, which are associated with a constitutively decreased pHi (19,20).…”

Section: Introductionmentioning

confidence: 99%

Intracellular pH Regulates Cancer and Stem Cell Behaviors: A Protein Dynamics Perspective

2020

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The International Society of Cancer Metabolism (ISCaM) meeting on Cancer Metabolic Rewiring, held in Braga Portugal in October 2019, provided an outstanding forum for investigators to present current findings and views, and discuss ideas and future directions on fundamental biology as well as clinical translations. The first session on Cancer pH Dynamics was preceded by the opening keynote presentation from our group entitled Intracellular pH Regulation of Protein Dynamics: From Cancer to Stem Cell Behaviors. In this review we introduce a brief background on intracellular pH (pHi) dynamics, including how it is regulated as well as functional consequences, summarize key findings included in our presentation, and conclude with perspectives on how understanding the role of pHi dynamics in stem cells can be relevant for understanding how pHi dynamics enables cancer progression.

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Section: Introductionmentioning

confidence: 99%

Intracellular pH Regulates Cancer and Stem Cell Behaviors: A Protein Dynamics Perspective

2020

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“…It has been reported that the Na + /H + -exchanger Nhe2 is responsible for an increase in pH i during prefollicular cell differentiation [6]. In addition, ae2, a Cl − /HCO 3 − -exchanger, was identified as a regulator of pH i in the FC lineage: Loss of ae2 resulted in reduced fertility, fewer ovarioles, reduced follicle number and reduced ovary size, suggesting that this phenotype is caused by dysregulation of pH i [6]. Data from our RNAi-screen indicate an impairment of ovary development and/or oogenesis after knockdown of the DEG/ENaC-subunit RPK, the V-ATPase-subunit Vha55, and the gap-junction subunits Inx1 and Inx3.…”

Section: Discussion V Mem -And Ph I -Changes In the Fe Revealed By Timentioning

confidence: 99%

“…According to both methods, the treatment with glibenclamide, furosemide or 9-anthroic acid resulted in alkalisation. Glibenclamide (ATP-sensitive K + -channels) is supposed to block H + -transport indirectly [ 16 , 35 ], while furosemide and 9-anthroic acid are expected to influence pH i via Cl − /HCO 3 − -antiport [ 6 , 16 , 53 , 54 ]. For concanamycin A, inhibiting V-ATPases [ 55 ], we observed alkalising effects in the FE.…”

Section: Discussionmentioning

confidence: 99%

“…The bMF in ork1 S10A show the same parallel alignment as in wt, however, in some areas (arrowheads), the bMF-cytoskeleton is weaker. During S10B and S12, ork1-follicles are characterised by a disturbed transversal transcellular bMF-alignment, resembling the kugelei mutant [22] for their role in developmental signalling and morphogenesis [6,30]. Microarray-expression data from the FlyAtlas database indicate highest expression levels for rpk in ovary and testis [30].…”

Section: Deg/enac-subunit Rpkmentioning

confidence: 99%

“…In recent years, bioelectrical signals have been shown to play decisive roles in regulating diverse cellular events [1][2][3][4][5][6]. For example, in Drosophila, a screen of 180 genes identified a variety of ion channels essential for normal wing development [7].…”

Section: Introductionmentioning

confidence: 99%

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Analysing bioelectrical phenomena in the Drosophila ovary with genetic tools: tissue-specific expression of sensors for membrane potential and intracellular pH, and RNAi-knockdown of mechanisms involved in ion exchange

Schotthöfer

Bohrmann

2020

BMC Dev Biol

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Background: Changes in transcellular bioelectrical patterns are known to play important roles during developmental and regenerative processes. The Drosophila follicular epithelium has proven to be an appropriate model system for studying the mechanisms by which bioelectrical signals emerge and act. Fluorescent indicator dyes in combination with various inhibitors of ion-transport mechanisms have been used to investigate the generation of membrane potentials (V mem) and intracellular pH (pH i). Both parameters as well as their anteroposterior and dorsoventral gradients were affected by the inhibitors which, in addition, led to alterations of microfilament and microtubule patterns equivalent to those observed during follicle-cell differentiation. Results: We expressed two genetically-encoded fluorescent sensors for V mem and pH i , ArcLight and pHluorin-Moesin, in the follicular epithelium of Drosophila. By means of the respective inhibitors, we obtained comparable effects on V mem and/or pH i as previously described for V mem-and pH i-sensitive fluorescent dyes. In a RNAiknockdown screen, five genes of ion-transport mechanisms and gap-junction subunits were identified exerting influence on ovary development and/or oogenesis. Loss of ovaries or small ovaries were the results of soma knockdowns of the innexins inx1 and inx3, and of the DEG/ENaC family member ripped pocket (rpk). Germline knockdown of rpk also resulted in smaller ovaries. Soma knockdown of the V-ATPase-subunit vha55 caused sizereduced ovaries with degenerating follicles from stage 10A onward. In addition, soma knockdown of the open rectifier K + channel 1 (ork1) resulted in a characteristic round-egg phenotype with altered microfilament and microtubule organisation in the follicular epithelium.

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Signal transduction in the early Drosophila follicle stem cell lineage

Rust¹,

Nystul²

2020

Current Opinion in Insect Science

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Drosophila anion exchanger 2 is required for proper ovary development and oogenesis

Cited by 11 publications

References 41 publications

Intracellular pH Regulates Cancer and Stem Cell Behaviors: A Protein Dynamics Perspective

Intracellular pH Regulates Cancer and Stem Cell Behaviors: A Protein Dynamics Perspective

Analysing bioelectrical phenomena in the Drosophila ovary with genetic tools: tissue-specific expression of sensors for membrane potential and intracellular pH, and RNAi-knockdown of mechanisms involved in ion exchange

Signal transduction in the early Drosophila follicle stem cell lineage

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