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LRP4 mutations, dental anomalies, and oral exostoses.
Int J Paediatr Dent
July 2024
National Biobank of Thailand, National Center for Genetic Engineering and Biotechnology (BIOTEC), Pathum Thani, Thailand.
Background: In order to generate a normal set of teeth, fine-tuning of Wnt/β-catenin signaling is required, in which WNT ligands bind to their inhibitors or WNT inhibitors bind to their co-receptors. Lrp4 regulates the number of teeth and their morphology by modulating Wnt/β-catenin signaling as a Wnt/β-catenin activator or inhibitor, depending on its interactions with the partner proteins, such as Sostdc1 and Dkk1.
Aim: To investigate genetic etiologies of dental anomalies involving LRP4 in a Thai cohort of 250 children and adults with dental anomalies.
The MuSK-BMP pathway regulates synaptic Nav1.4 localization and muscle excitability.
bioRxiv
October 2023
Carney Institute for Brain Science, Brown University, Providence, RI 02912.
The neuromuscular junction (NMJ) is the linchpin of nerve-evoked muscle contraction. Broadly considered, the function of the NMJ is to transduce a nerve action potential into a muscle fiber action potential (MFAP). Efficient information transfer requires both cholinergic signaling, responsible for the generation of endplate potentials (EPPs), and excitation, the activation of postsynaptic voltage-gated sodium channels (Nav1.
View Article and Find Full Text PDFThe collagen ColQ binds to LRP4 and regulates the activation of the Muscle-Specific Kinase-LRP4 receptor complex by agrin at the neuromuscular junction.
J Biol Chem
August 2023
Université Paris Cité, CNRS, Saints-Pères Paris Institute for the Neurosciences, Paris, France. Electronic address:
Collagen Q (ColQ) is a nonfibrillar collagen that plays a crucial role at the vertebrate neuromuscular junction (NMJ) by anchoring acetylcholinesterase to the synapse. ColQ also functions in signaling, as it regulates acetylcholine receptor clustering and synaptic gene expression, in a manner dependent on muscle-specific kinase (MuSK), a key protein in NMJ formation and maintenance. MuSK forms a complex with low-density lipoprotein receptor-related protein 4 (LRP4), its coreceptor for the proteoglycan agrin at the NMJ.
View Article and Find Full Text PDFStructural insights into the assembly of the agrin/LRP4/MuSK signaling complex.
Proc Natl Acad Sci U S A
June 2023
Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390.
MuSK is a receptor tyrosine kinase (RTK) that plays essential roles in the formation and maintenance of the neuromuscular junction. Distinct from most members of RTK family, MuSK activation requires not only its cognate ligand agrin but also its coreceptors LRP4. However, how agrin and LRP4 coactivate MuSK remains unclear.
View Article and Find Full Text PDFBalancing WNT signalling in early forebrain development: The role of LRP4 as a modulator of LRP6 function.
Front Cell Dev Biol
April 2023
Neuroscience, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
The specification of the forebrain relies on the precise regulation of WNT/ß-catenin signalling to support neuronal progenitor cell expansion, patterning, and morphogenesis. Imbalances in WNT signalling activity in the early neuroepithelium lead to congenital disorders, such as neural tube defects (NTDs). LDL receptor-related protein (LRP) family members, including the well-studied receptors LRP5 and LRP6, play critical roles in modulating WNT signalling capacity through tightly regulated interactions with their co-receptor Frizzled, WNT ligands, inhibitors and intracellular WNT pathway components.
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