Sonic hedgehog (Shh) signaling plays a crucial role in growth and patterning during embryonic development, and also in stem cell maintenance and tissue regeneration in adults. Aberrant Shh pathway activation is involved in the development of many tumors, and one of the most affected Shh signaling steps found in these tumors is the regulation of the signaling receptor Smoothened by the Shh receptor Patched. In the present work, we investigated Patched activity and the mechanism by which Patched inhibits Smoothened. Using the well-known Shh-responding cell line of mouse fibroblasts NIH 3T3, we first observed that enhancement of the intracellular cholesterol concentration induces Smoothened enrichment in the plasma membrane, which is a crucial step for the signaling activation. We found that binding of Shh protein to its receptor Patched, which involves Patched internalization, increases the intracellular concentration of cholesterol and decreases the efflux of a fluorescent cholesterol derivative (BODIPY-cholesterol) from these cells. Treatment of fibroblasts with cyclopamine, an antagonist of Shh signaling, inhibits Patched expression and reduces BODIPY-cholesterol efflux, while treatment with the Shh pathway agonist SAG enhance...Continue Reading
Use of chemical chaperones in the yeast Saccharomyces cerevisiae to enhance heterologous membrane protein expression: high-yield expression and purification of human P-glycoprotein
Hedgehog induces opposite changes in turnover and subcellular localization of patched and smoothened
The sterol-sensing domain of Patched protein seems to control Smoothened activity through Patched vesicular trafficking
Mutations in the sterol-sensing domain of Patched suggest a role for vesicular trafficking in Smoothened regulation
Role of the cholesterol biosynthetic pathway in osteoblastic differentiation of marrow stromal cells
Modeling and mutagenesis of the binding site of Calhex 231, a novel negative allosteric modulator of the extracellular Ca(2+)-sensing receptor
Niemann-Pick C1 Like 1 (NPC1L1) is the intestinal phytosterol and cholesterol transporter and a key modulator of whole-body cholesterol homeostasis.
Gas chromatographic separation and mass spectrometric identification of mixtures of oxyphytosterol and oxycholesterol derivatives application to a phytosterol-enriched food
Hedgehog signalling activity of Smoothened requires phosphorylation by protein kinase A and casein kinase I
Human receptor Smoothened, a mediator of Hedgehog signalling, expressed in its native conformation in yeast
Signaling from Smo to Ci/Gli: conservation and divergence of Hedgehog pathways from Drosophila to vertebrates
Human receptors patched and smoothened partially transduce hedgehog signal when expressed in Drosophila cells
Purified NPC1 protein. I. Binding of cholesterol and oxysterols to a 1278-amino acid membrane protein
Functional studies of membrane-bound and purified human Hedgehog receptor Patched expressed in yeast
A reflection of the lasting contributions from Dr. Robert Bittman to sterol trafficking, sphingolipid and phospholipid research.
A marked paucity of granule cells in the developing cerebellum of the Npc1(-/-) mouse is corrected by a single injection of hydroxypropyl-β-cyclodextrin
Visualization of lipid metabolism in the zebrafish intestine reveals a relationship between NPC1L1-mediated cholesterol uptake and dietary fatty acid.
Analysis of hedgehog signaling in cerebellar granule cell precursors in a conditional Nsdhl allele demonstrates an essential role for cholesterol in postnatal CNS development
Lung fibroblasts share mesenchymal stem cell features which are altered in chronic obstructive pulmonary disease via the overactivation of the Hedgehog signaling pathway
Targeting the multidrug transporter Patched potentiates chemotherapy efficiency on adrenocortical carcinoma in vitro and in vivo
Synthesis of cholesterol analogues bearing BODIPY fluorophores by Suzuki or Liebeskind-Srogl cross-coupling and evaluation of their potential for visualization of cholesterol pools.
Reply to "measuring polymyxin uptake by renal tubular cells: is BODIPY-polymyxin B an appropriate probe?"
Discovery, molecular and pharmacological characterization of GSA-10, a novel small-molecule positive modulator of Smoothened
NPC1 Deficiency in Mice is Associated with Fetal Growth Restriction, Neonatal Lethality and Abnormal Lung Pathology
BODIPY-cholesterol can be reliably used to monitor cholesterol efflux from capacitating mammalian spermatozoa
Engineered biomimetic nanoparticle for dual targeting of the cancer stem-like cell population in sonic hedgehog medulloblastoma.
The pathogenesis of lysosomal storage disorders: beyond the engorgement of lysosomes to abnormal development and neuroinflammation
Targeting Smoothened as a New Frontier in the Functional Recovery of Central Nervous System Demyelinating Pathologies
Astemizole Sensitizes Adrenocortical Carcinoma Cells to Doxorubicin by Inhibiting Patched Drug Efflux Activity
Natural paniceins from mediterranean sponge inhibit the multidrug resistance activity of Patched and increase chemotherapy efficiency on melanoma cells
Maintenance of Membrane Integrity and Permeability Depends on a Patched-Related Protein in Caenorhabditis elegans
Shortened primary cilium length and dysregulated Sonic hedgehog signaling in Niemann-Pick C1 disease
Inhibition of Patched Drug Efflux Increases Vemurafenib Effectiveness against Resistant BrafV600E Melanoma
Sterol Characteristics in Silkworm Brain and Various Tissues Characterized by Precise Sterol Profiling Using LC-MS/MS
Molecular insights into the Patched1 drug efflux inhibitory activity of panicein A hydroquinone: a computational study.
Gpr37l1/prosaposin receptor regulates Ptch1 trafficking, Shh production, and cell proliferation in cerebellar primary astrocytes
Caenorhabditis elegans PTR/PTCHD PTR-18 promotes the clearance of extracellular hedgehog-related protein via endocytosis.
Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.