title: Lrp4 domains differentially regulate limb/brain development and synaptic plasticity.
abstract: Apolipoprotein E (ApoE) genotype is the strongest predictor of Alzheimer's Disease (AD) risk. ApoE is a cholesterol transport protein that binds to members of the Low-Density Lipoprotein (LDL) Receptor family, which includes LDL Receptor Related Protein 4 (Lrp4). Lrp4, together with one of its ligands Agrin and its co-receptors Muscle Specific Kinase (MuSK) and Amyloid Precursor Protein (APP), regulates neuromuscular junction (NMJ) formation. All four proteins are also expressed in the adult brain, and APP, MuSK, and Agrin are required for normal synapse function in the CNS. Here, we show that Lrp4 is also required for normal hippocampal plasticity. In contrast to the closely related Lrp8/Apoer2, the intracellular domain of Lrp4 does not appear to be necessary for normal expression and maintenance of long-term potentiation at central synapses or for the formation and maintenance of peripheral NMJs. However, it does play a role in limb development.
authors: Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, United States of America; Center for Translational Neurodegeneration Research, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, United States of America.
authors: Theresa
authors: T
authors: Pohlkamp
authors: Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, United States of America; Center for Translational Neurodegeneration Research, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, United States of America.
authors: Murat
authors: M
authors: Durakoglugil
authors: Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, United States of America; Center for Translational Neurodegeneration Research, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, United States of America.
authors: Courtney
authors: C
authors: Lane-Donovan
authors: Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, United States of America; Center for Translational Neurodegeneration Research, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, United States of America.
authors: Xunde
authors: X
authors: Xian
authors: Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, United States of America.
authors: Eric B
authors: EB
authors: Johnson
authors: Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, United States of America.
authors: Robert E
authors: RE
authors: Hammer
authors: Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, United States of America; Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, United States of America; Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, United States of America; Center for Translational Neurodegeneration Research, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, United States of America.
authors: Joachim
authors: J
authors: Herz
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology*; D005121:Extremities / Q000196:embryology*; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000737:chemistry / Q000235:genetics*; D017880:Limb Deformities, Congenital / Q000235:genetics; D017774:Long-Term Potentiation / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation; D009473:Neuronal Plasticity / Q000235:genetics*; D038081:Organogenesis / Q000235:genetics*; D010641:Phenotype; D054730:Protein Interaction Domains and Motifs / Q000235:genetics*
chemical_list: D026502:LDL-Receptor Related Proteins; C551781:LRP4 protein, human