RapC Is Involved in the Development of Dictyostelium Through the Regulation of Autophagy and Calcium Signaling
- 1Department of Integrative Biological Sciences & BK21 FOUR Educational Research Group for Age-Associated Disorder Control Technology, Chosun University, Gwangju 61452, Republic of Korea
- 2The Basic Science Institute of Chosun University, Chosun University, Gwangju 61452, Republic of Korea
Abstract
RapC is a Rap-subfamily small GTPase in Dictyostelium whose developmental function remains largely uncharacterized. Upon starvation, individual amoebae aggregate and undergo morphogenetic transitions to ultimately produce a fruiting body, a process requiring precise spatiotemporal regulation of a single apical tip as the primary organizing center. Here, we report that RapC is required for tip organizer formation during multicellular development by modulating autophagy and intracellular calcium signaling. rapC null cells develop normally through aggregation but consistently form three to four apical tips per aggregate rather than the single organizer tip characteristic of wild-type cells. Pharmacological phenocopy experiments revealed that caffeine and the selective TORC1 inhibitor rapamycin recapitulate the multi-tip phenotype, whereas the PI3K inhibitor LY294002 and the pan-TOR inhibitor Torin2 do not, implicating TORC1 signaling as the relevant downstream effector. In line with this, rapC null cells exhibit normal GFP-PH:CRAC translocation kinetics and slightly elevated PKB/PKBR1 phosphorylation, ruling out defects in the PI3K–TORC2–PKB signaling axis. Instead, rapC null cells display markedly elevated autophagic flux as assessed by the tandem RFP-GFP-Atg8 reporter assay, consistent with attenuated TORC1-mediated autophagy suppression. Furthermore, aggregation-competent rapC null cells show increased intracellular calcium ([Ca2+]i) upon external calcium stimulation, a response absent in wild-type cells and not reproduced by rapamycin, indicating a TORC1-independent role for RapC in calcium homeostasis. Together, our findings establish that RapC promotes normal Dictyostelium development by supporting TORC1 activity to suppress excessive autophagic flux and by maintaining [Ca2+]i homeostasis through a TORC1-independent mechanism.
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BibTeX
@article{han2026rapc,
title = {{RapC Is Involved in the Development of Dictyostelium Through the Regulation of Autophagy and Calcium Signaling}},
author = {Nara Han and Uri Han and Dahyeon Kim and Wonbum Kim and Taeck Joong Jeon},
journal = {Cells},
year = {2026},
month = oct,
doi = {10.3390/cells15201878},
url = {https://www.mdpi.com/2073-4409/15/20/1878},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - RapC Is Involved in the Development of Dictyostelium Through the Regulation of Autophagy and Calcium Signaling
AU - Nara Han
AU - Uri Han
AU - Dahyeon Kim
AU - Wonbum Kim
AU - Taeck Joong Jeon
PY - 2026
DA - 2026/10/15
JO - Cells
DO - 10.3390/cells15201878
UR - https://www.mdpi.com/2073-4409/15/20/1878
AB - RapC is a Rap-subfamily small GTPase in Dictyostelium whose developmental function remains largely uncharacterized. Upon starvation, individual amoebae aggregate and undergo morphogenetic transitions to ultimately produce a fruiting body, a process requiring precise spatiotemporal regulation of a single apical tip as the primary organizing center. Here, we report that RapC is required for tip organizer formation during multicellular development by modulating autophagy and intracellular calcium signaling. rapC null cells develop normally through aggregation but consistently form three to four apical tips per aggregate rather than the single organizer tip characteristic of wild-type cells. Pharmacological phenocopy experiments revealed that caffeine and the selective TORC1 inhibitor rapamycin recapitulate the multi-tip phenotype, whereas the PI3K inhibitor LY294002 and the pan-TOR inhibitor Torin2 do not, implicating TORC1 signaling as the relevant downstream effector. In line with this, rapC null cells exhibit normal GFP-PH:CRAC translocation kinetics and slightly elevated PKB/PKBR1 phosphorylation, ruling out defects in the PI3K–TORC2–PKB signaling axis. Instead, rapC null cells display markedly elevated autophagic flux as assessed by the tandem RFP-GFP-Atg8 reporter assay, consistent with attenuated TORC1-mediated autophagy suppression. Furthermore, aggregation-competent rapC null cells show increased intracellular calcium ([Ca2+]i) upon external calcium stimulation, a response absent in wild-type cells and not reproduced by rapamycin, indicating a TORC1-independent role for RapC in calcium homeostasis. Together, our findings establish that RapC promotes normal Dictyostelium development by supporting TORC1 activity to suppress excessive autophagic flux and by maintaining [Ca2+]i homeostasis through a TORC1-independent mechanism.
SN - 2073-4409
ER -