Two types of store-operated Ca2+ channels with different activation modes and molecular origin in LNCaP human

Fabien Vanden Abeele1, Loic Lemonnier, Stéphanie Thébault

  • 1Laboratoire de Physiologie Cellulaire, INSERM EMI-0228, Université des Sciences et Technologies de Lille, Bat. SN3, 59655 Villeneuve d'Ascq, France.

Insights

Two distinct types of store-operated calcium channels (SOCs) were identified in prostate cancer cells. These channels differ in their activation mechanisms and store depletion sensitivity, offering new insights into calcium signaling.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Calcium Signaling

Background:

  • The precise mechanisms coupling store-operated channels (SOCs) to endoplasmic reticulum (ER) calcium (Ca2+) store depletion remain unclear.
  • The molecular identity of SOCs themselves is not fully elucidated.

Purpose of the Study:

  • To investigate the molecular identity and activation mechanisms of SOCs in LNCaP prostate cancer cells.
  • To differentiate between distinct SOC populations and their relationship to ER Ca2+ store depletion.

Main Methods:

  • Utilized LNCaP prostate cancer epithelial cells.
  • Investigated SOC activation via inositol 1,4,5-trisphosphate (IP3)-mediated and thapsigargin-facilitated ER store depletion.
  • Analyzed the contribution of TRPC1, TRPC4, and TRPV6 to SOC function.

Main Results:

  • Demonstrated the co-existence of two molecularly distinct endogenous SOC populations in LNCaP cells.
  • Identified SOC(CC) (conformational coupling) activated by IP3 receptors and TRPC1, and SOC(CIF) (calcium influx factor) activated by Ca2+-independent phospholipase A2 and TRPC4.
  • TRPV6 was found to play a role in both SOC populations.

Conclusions:

  • These findings reveal novel insights into the heterogeneity of SOCs within a single cell type.
  • The results reconcile current hypotheses regarding SOC activation mechanisms and provide a clearer understanding of their molecular basis.

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