dSmad2 differentially regulates dILP2 and dILP5 in insulin producing and circadian pacemaker cells in unmated adult females.
dSmad2 differentially regulates dILP2 and dILP5 in insulin producing and circadian pacemaker cells in unmated adult females.
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DOI：
10.1371/journal.pone.0280529
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发表时间：
2023
期刊：
影响因子：
3.7
通讯作者：
Newfeld, Stuart J. J.
中科院分区：
文献类型：
--
作者：
Goldsmith, Samuel L. L.;Newfeld, Stuart J. J.
关于环境对代谢和全身胰岛素水平的影响已经知道很多。关于这些影响如何转化为调节胰岛素产生的分子机制，我们知之甚少。为了更好地理解分子机制，我们在未交配的成年雌性果蝇中产生了标记的细胞，这些细胞对于果蝇TGF-β信号转导子dSmad 2中的无效突变是纯合的。然后，我们进行并排的单细胞比较的像素强度的两个果蝇胰岛素样肽（dILP 2和dILP 5）在dSmad 2突变体和野生型胰岛素产生细胞（IPC）。分析揭示了dSmad 2调节dILP的多种特征。此外，我们发现dILP 5在昼夜节律起搏细胞（CPC）中表达并受dSmad 2调节。dSmad 2调节的结果在IPC内dILP 2和dILP 5之间不同，在IPC和CPC之间dILP 5不同。dILP 2和dILP 5之间的dSmad 2调节模式不同。dSmad 2对IPC中dILP 2的拮抗作用是稳健的，但dSmad 2对IPC和CPC中dILP 5的调节取决于dSmad 2剂量而在拮抗作用和激动作用之间切换。dCORL突变体（Flybase中的fussel和哺乳动物中的SKOR）和upd 2突变体未交配的成年雌性的IPC中dILP 2和dILP 5的伴随研究显示与野生型没有显著差异。总之，数据表明，dSmad 2调节dILP 2和dILP 5通过不同的机制，在IPC（拮抗剂）和CPC（激动剂）和未交配的成年女性，dSmad 2的作用独立于dCORL和upd 2。
Much is known about environmental influences on metabolism and systemic insulin levels. Less is known about how those influences are translated into molecular mechanisms regulating insulin production. To better understand the molecular mechanisms we generated marked cells homozygous for a null mutation in the Drosophila TGF-β signal transducer dSmad2 in unmated adult females. We then conducted side-by-side single cell comparisons of the pixel intensity of two Drosophila insulin-like peptides (dILP2 and dILP5) in dSmad2- mutant and wild type insulin producing cells (IPCs). The analysis revealed multiple features of dSmad2 regulation of dILPs. In addition, we discovered that dILP5 is expressed and regulated by dSmad2 in circadian pacemaker cells (CPCs). Outcomes of regulation by dSmad2 differ between dILP2 and dILP5 within IPCs and differ for dILP5 between IPCs and CPCs. Modes of dSmad2 regulation differ between dILP2 and dILP5. dSmad2 antagonism of dILP2 in IPCs is robust but dSmad2 regulation of dILP5 in IPCs and CPCs toggles between antagonism and agonism depending upon dSmad2 dosage. Companion studies of dILP2 and dILP5 in the IPCs of dCORL mutant (fussel in Flybase and SKOR in mammals) and upd2 mutant unmated adult females showed no significant difference from wild type. Taken together, the data suggest that dSmad2 regulates dILP2 and dILP5 via distinct mechanisms in IPCs (antagonist) and CPCs (agonist) and in unmated adult females that dSmad2 acts independently of dCORL and upd2.
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影响因子：
3.3
作者：
Takaesu, Norma T.;Hyman-Walsh, Cathy;Newfeld, Stuart J.
通讯作者：
Newfeld, Stuart J.
影响因子：
64.5
作者：
Rajan A;Perrimon N
通讯作者：
Perrimon N
DOI：
10.1093/g3journal/jkac019
发表时间：
2022-04-04
期刊：
G3 (Bethesda, Md.)
影响因子：
--
作者：
Goldsmith SL;Shimell M;Tauscher P;Daly SM;Shimmi O;O'Connor MB;Newfeld SJ
通讯作者：
Newfeld SJ
影响因子：
7.2
作者：
Stanley A;Tichy ED;Kocan J;Roberts DW;Shore EM;Mourkioti F
通讯作者：
Mourkioti F
影响因子：
2.7
作者：
Hombría, JCG;Brown, S;Zeidler, MP
通讯作者：
Zeidler, MP