Rho GTPase

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Rho GTPase is a family of enzymes belonging to the Ras superfamily of monomeric G proteins. These enzymes are involved in the regulation of many aspects of intracellular signaling pathways, especially those controlling the dynamics of the actin cytoskeleton. Due to their role in actin organization, Rho GTPases are crucial for processes such as cell migration, cell division, and cell cycle progression.

Function[edit | edit source]

Rho GTPases act as molecular switches in the cell, cycling between an active GTP-bound state and an inactive GDP-bound state. This cycle is regulated by three main types of regulatory proteins: Guanine nucleotide exchange factors (GEFs), which facilitate the exchange of GDP for GTP; GTPase-activating proteins (GAPs), which increase the GTP hydrolysis rate; and Guanine nucleotide dissociation inhibitors (GDIs), which sequester Rho GTPases in the cytosol.

The activation of Rho GTPases triggers a variety of downstream effects, primarily through the influence on actin cytoskeleton organization. For example, RhoA promotes the formation of stress fibers and focal adhesions, Rac1 induces the formation of lamellipodia, and Cdc42 is involved in the formation of filopodia.

Types[edit | edit source]

There are several members of the Rho GTPase family, including:

  • RhoA, which is involved in the formation of stress fibers and focal adhesions.
  • Rac1, which promotes the formation of lamellipodia at the leading edge of migrating cells.
  • Cdc42, which controls the formation of filopodia.

Clinical Significance[edit | edit source]

Rho GTPases are implicated in various human diseases. Their abnormal regulation has been linked to diseases such as cancer, where they can affect cell proliferation, apoptosis, and metastasis. Inhibitors of Rho GTPases are being studied as potential therapeutic agents in cancer treatment.

Research[edit | edit source]

Research on Rho GTPases continues to uncover their complex roles in cell biology and their potential as targets for therapeutic intervention in disease. Studies often focus on the development of specific inhibitors that can modulate the activity of Rho GTPases in a controlled manner.

See Also[edit | edit source]

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Contributors: Prab R. Tumpati, MD