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A Novel Role of the TRPM4 Ion Channel in Exocytosis
Paulina Stokłosa1, Sven Kappel1, Christine Peinelt1
1Institute of Biochemistry and Molecular Medicine, University of Bern, 3012 Bern, Switzerland.
Abstract:
Under physiological conditions, the widely expressed calcium-activated TRPM4 channel conducts sodium into cells. This sodium influx depolarizes the plasma membrane and reduces the driving force for calcium entry. The aberrant expression or function of TRPM4 has been reported in various diseases, including different types of cancer. TRPM4 is mainly localized in the plasma membrane, but it is also found in intracellular vesicles, which can undergo exocytosis. In this study, we show that calcium-induced exocytosis in the colorectal cancer cell line HCT116 is dependent on TRPM4. In addition, the findings from some studies of prostate cancer cell lines suggest a more general role of TRPM4 in calcium-induced exocytosis in cancer cells. Furthermore, calcium-induced exocytosis depends on TRPM4 ion conductivity. Additionally, an increase in intracellular calcium results in the delivery of TRPM4 to the plasma membrane. This process also depends on TRPM4 ion conductivity. TRPM4-dependent exocytosis and the delivery of TRPM4 to the plasma membrane are mediated by SNARE proteins. Finally, we provide evidence that calcium-induced exocytosis depends on TRPM4 ion conductivity, not within the plasma membrane, but rather in TRPM4-containing vesicles.
Insights
Calcium-activated TRPM4 channels regulate exocytosis in cancer cells. This process, crucial for cancer progression, depends on TRPM4
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Transient Receptor Potential Melastatin 4 (TRPM4) channels are calcium-activated, sodium-conducting channels widely expressed in cells.
- Aberrant TRPM4 expression or function is implicated in various diseases, notably different types of cancer.
- TRPM4 localizes to the plasma membrane and intracellular vesicles, with vesicles capable of exocytosis.
Purpose of the Study:
- To investigate the role of TRPM4 in calcium-induced exocytosis in cancer cells.
- To determine if TRPM4 ion conductivity is essential for calcium-induced exocytosis and TRPM4 trafficking.
Main Methods:
- Utilized colorectal cancer cell line HCT116 and prostate cancer cell lines.
- Investigated calcium-induced exocytosis and TRPM4 localization.
- Assessed the dependence of these processes on TRPM4 ion conductivity and SNARE proteins.
Main Results:
- Calcium-induced exocytosis in HCT116 cells is dependent on TRPM4.
- TRPM4 ion conductivity is essential for calcium-induced exocytosis and the delivery of TRPM4 to the plasma membrane.
- TRPM4-dependent exocytosis and membrane delivery are mediated by SNARE proteins, with conductivity occurring within vesicles.
Conclusions:
- TRPM4 plays a critical role in calcium-induced exocytosis in cancer cells, particularly in colorectal and prostate cancer.
- TRPM4 ion conductivity, localized within intracellular vesicles, is essential for regulating exocytosis and its own plasma membrane delivery.
- SNARE proteins mediate TRPM4-dependent exocytosis, highlighting TRPM4 as a potential therapeutic target in cancer.
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