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Introduction

Lysophosphatidic Acid Receptor 1 (commonly referred to as LPA1) is a G-protein coupled receptor and one of 6 different LPA receptors (LPA1-LPA6) that bind the phospholipid derivative lysophosphatidic acid (LPA), a signaling molecule that acts as a potent mitogen upon binding to one of the six receptors. ----------- LPA1 is part of the larger EDG receptor family(link) which includes the more widely known sphingosine 1-phopshate receptors.

Structure

The LPA1 receptor protein is composed of 364 amino acids with a mass of approximately 41 kDa. Just as other G-protein coupled receptors, LPA1 contains seven alpha helices which make up the seven transmembrane spanning domains with three intracellular loops and three extracellular loops. Within these helices is an amphiphilic binding pocket enabling the LPA molecule to bind.

Key Ligand Interactions

Three separate interactions an antagonist of LPA1, ON7, help demonstrate the key interactions that stabilize the binding of the LPA phospholipid to this receptor.

Function

The LPA1 receptor has been found to initiate downstream signaling cascades with three Galpha(link) proteins that signal for cell proliferation, survival, and migration. Because of the signaling activity of LPA1, abnormal expression has been linked to tumor growth, survival, and migration. The LPA1 receptor is present in nearly all cells and tissues throughout the body, and deletion of the LPA1 receptor has been found to have physiological effects on every organ system. Despite this receptor being expressed throughout the body, LPA1 has been found to be expressed highly in neural tissue, aiding in Schwann cell migration and myelination, formation of synapses, and glial cell growth.

Disease Relevance

Receptor Comparison

Sphingosine 1-Phosphate Receptor

Endocannabinoid Receptor 1

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