GPER-L2

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Introduction

GPER-L2 (G Protein-Coupled Estrogen Receptor 2) is a member of the G protein-coupled receptor (GPCR) family, which is involved in mediating the effects of estrogen in various tissues. This receptor is distinct from the classical nuclear estrogen receptors, ERα and ERβ, and is primarily located on the cell membrane, where it can rapidly activate intracellular signaling pathways.

Structure

GPER-L2 is a transmembrane protein that spans the cell membrane seven times, a characteristic feature of GPCRs. The receptor is composed of an extracellular N-terminus, seven transmembrane helices, and an intracellular C-terminus. The binding of estrogen to GPER-L2 induces a conformational change that activates associated G proteins, leading to downstream signaling events.

Function

GPER-L2 plays a crucial role in mediating non-genomic signaling pathways of estrogen. Upon activation by estrogen, GPER-L2 can:

  • Activate adenylate cyclase, increasing intracellular cAMP levels.
  • Stimulate the release of calcium ions from intracellular stores.
  • Activate the PI3K/Akt and MAPK/ERK signaling pathways.

These pathways are involved in various cellular processes, including cell proliferation, apoptosis, and migration. GPER-L2 is implicated in cardiovascular function, neuroprotection, and cancer progression.

Clinical Significance

GPER-L2 has been studied for its role in various diseases:

  • Cardiovascular Disease: GPER-L2 activation has been shown to have protective effects on the cardiovascular system, including vasodilation and anti-inflammatory effects.
  • Cancer: GPER-L2 is expressed in several types of cancer, including breast and ovarian cancer. It may contribute to cancer cell proliferation and metastasis.
  • Neuroprotection: GPER-L2 activation has neuroprotective effects, potentially offering therapeutic benefits in neurodegenerative diseases.

Research and Development

Ongoing research is focused on developing selective agonists and antagonists for GPER-L2 to better understand its role in health and disease. These compounds could serve as potential therapeutic agents for conditions where GPER-L2 is implicated.

Also see

References


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Contributors: Prab R. Tumpati, MD