Deletion of Dictyostelium tpc2 gene forms multi-tipped structures, regulates autophagy and cell-type patterning

IF 2.4 4区生物学 Q4 CELL BIOLOGY

Biology of the Cell Pub Date : 2024-03-27 DOI:10.1111/boc.202300067

Madhubala Rathore, Ashima Thakur, Shweta Saran

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引用次数: 0

Abstract

Background Information

Two pore channels (TPCs) are voltage-gated ion channel superfamily members that release Ca²⁺ from acidic intracellular stores and are ubiquitously present in both animals and plants. Starvation initiates multicellular development in Dictyostelium discoideum. Increased intracellular calcium levels bias Dictyostelium cells towards the stalk pathway and thus we decided to analyze the role of TPC2 in development, differentiation, and autophagy.

Results

We showed TPC2 protein localizes in lysosome-like acidic vesicles and the in situ data showed stalk cell biasness. Deletion of tpc2 showed defective and delayed development with formation of multi-tipped structures attached to a common base, while tpc2^OE cells showed faster development with numerous small-sized aggregates and wiry fruiting bodies. The tpc2^OE cells showed higher intracellular cAMP levels as compared to the tpc2⁻ cells while pinocytosis was found to be higher in the tpc2⁻ cells. Also, TPC2 regulates cell-substrate adhesion and cellular morphology. Under nutrient starvation, deletion of tpc2 reduced autophagic flux as compared to Ax2. During chimera formation, tpc2⁻ cells showed a bias towards the prestalk/stalk region while tpc2^OE cells showed a bias towards the prespore/spore region. tpc2 deficient strain exhibits aberrant cell-type patterning and loss of distinct boundary between the prestalk/prespore regions.

Conclusion

TPC2 is required for effective development and differentiation in Dictyostelium and supports autophagic cell death and cell-type patterning.

Significance

Decreased calcium due to deletion of tpc2 inhibit autophagic flux.

Abstract Image

查看原文本刊更多论文

竹荪 tpc2 基因缺失会形成多尖端结构，调节自噬和细胞类型模式化。

背景信息：双孔通道（TPCs）是电压门控离子通道超家族成员，可从酸性细胞内贮存释放 Ca2+，在动物和植物中普遍存在。饥饿启动了盘基竹荪的多细胞发育。细胞内钙含量的增加会使竹荪细胞偏向茎途径，因此我们决定分析 TPC2 在发育、分化和自噬中的作用：结果：我们发现TPC2蛋白定位于溶酶体样酸性囊泡中，原位数据显示了柄细胞的偏向性。缺失 tpc2 的细胞发育缺陷和延迟，会形成连接到一个共同基部的多尖结构，而 tpc2OE 细胞则发育较快，会形成许多小尺寸的聚集体和毛状子实体。与 tpc2-细胞相比，tpc2OE 细胞显示出更高的细胞内 cAMP 水平，同时发现 tpc2-细胞的针状细胞增多。此外，TPC2 还调节细胞与基质的粘附和细胞形态。在营养饥饿条件下，与Ax2相比，缺失tpc2会降低自噬通量。在嵌合体形成过程中，tpc2-细胞偏向于前柄/柄区，而tpc2OE细胞偏向于前孢子/孢子区：结论：TPC2 是竹荪有效发育和分化所必需的，并支持自噬细胞死亡和细胞类型模式化：意义：tpc2缺失导致的钙质减少会抑制自噬通量。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biology of the Cell 生物-细胞生物学

CiteScore

5.30

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： The journal publishes original research articles and reviews on all aspects of cellular, molecular and structural biology, developmental biology, cell physiology and evolution. It will publish articles or reviews contributing to the understanding of the elementary biochemical and biophysical principles of live matter organization from the molecular, cellular and tissues scales and organisms. This includes contributions directed towards understanding biochemical and biophysical mechanisms, structure-function relationships with respect to basic cell and tissue functions, development, development/evolution relationship, morphogenesis, stem cell biology, cell biology of disease, plant cell biology, as well as contributions directed toward understanding integrated processes at the organelles, cell and tissue levels. Contributions using approaches such as high resolution imaging, live imaging, quantitative cell biology and integrated biology; as well as those using innovative genetic and epigenetic technologies, ex-vivo tissue engineering, cellular, tissue and integrated functional analysis, and quantitative biology and modeling to demonstrate original biological principles are encouraged.