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Related Concept Videos

Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
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Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
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During fertilization, an egg and sperm cell fuse to create a new diploid structure. In humans, the process occurs once the egg has been released from the ovary, and travels into the fallopian tubes. The process requires several key steps: 1) sperm present in the genital tract must locate the egg; 2) once there, sperm need to release enzymes to help them burrow through the protective zona pellucida of the egg; and 3) the membranes of a single sperm cell and egg must fuse, with the sperm...
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Positive Regulator Molecules

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Positive Regulator Molecules

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Calmodulin-driven nuclear entry: trigger for sex determination and terminal differentiation.

John A Hanover1, Dona C Love, William A Prinz

  • 1Laboratory of Cell Biochemistry and Biology, NIDDK, NIH, Bethesda, MD 20892, USA. jah@helix.nih.gov

The Journal of Biological Chemistry
|January 8, 2009
PubMed
Summary

Calcium-calmodulin facilitates nuclear entry for key transcription factors, distinct from the standard pathway. This process is vital for male gonad development and cell differentiation.

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • A novel nuclear entry pathway mediated by calcium-calmodulin was previously proposed, distinct from the canonical Ran-dependent pathway.
  • This pathway is now understood to be crucial for delivering architectural transcription factors to chromatin.

Purpose of the Study:

  • To explore the role of calcium-calmodulin-mediated nuclear import in cellular processes.
  • To investigate the implications of defects in this pathway for human development and disease.

Main Methods:

  • The study builds upon previous work proposing the calcium-calmodulin nuclear entry pathway.
  • Analysis of existing research and clinical data regarding transcription factor import and its consequences.

Main Results:

  • Calcium-calmodulin-driven nuclear entry facilitates the delivery of architectural transcription factors to chromatin.
  • Defects in this import pathway for SRY and SOX9 transcription factors in Sertoli cells are linked to human sex reversal diseases and altered male gonad development.
  • This nuclear entry mechanism is conserved across eukaryotes, from yeast to humans.

Conclusions:

  • Calcium-calmodulin-triggered nuclear entry is an evolutionarily ancient and vital process.
  • It plays a significant role in the nuclear import of key architectural transcription factors.
  • This pathway is a potential epigenetic regulator of terminal differentiation, responding to cell signaling and impacting gonad development.