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Related Concept Videos

Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

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Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
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Mechanism of Filopodia Formation01:39

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Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
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Mechanism of Ciliary Motion01:05

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The ciliary structures were first seen in 1647 by Antonie Leeuwenhoek while observing the protozoans. In lower organisms, these appendages are responsible for cell movement, while in higher organisms, these appendages help in the movement of the extracellular fluids within the body cavities.
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Microtubules in Signaling01:22

Microtubules in Signaling

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The primary cilium, made up of microtubules, acts as antennae on the cell surfaces for relaying external stimuli into the cells. These fine hair-like structures are present, generally one per cell. These are non-motile cilia in a 9+0 microtubules arrangement, where the central pair of microtubules are absent. The primary cilia arise from the basal body embedded in the cell membrane. Intraflagellar transport (IFT) carries requisite proteins from the cytoplasm to the cilium because the primary...
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IP3/DAG Signaling Pathway01:11

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Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
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Microtubule Associated Motor Proteins01:32

Microtubule Associated Motor Proteins

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Eukaryotic cells have different motor proteins for transporting various cargo within the cell. These motor proteins differ based on the filament they associate with, the direction they move within the cell, and the type of cargo they transport. Motor proteins that associate with microtubules are known as microtubule-associated motor proteins. There are two families of microtubule-associated motor proteins —Kinesins and Dyneins. Both these proteins assist in the transport of cellular...
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Related Experiment Video

Updated: Mar 9, 2026

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry
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Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry

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INPP5E regulates phosphoinositide-dependent cilia transition zone function.

Jennifer M Dyson1, Sarah E Conduit1, Sandra J Feeney1

  • 1Cancer Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.

The Journal of Cell Biology
|December 22, 2016
PubMed
Summary
This summary is machine-generated.

Inositol polyphosphate 5-phosphatase INPP5E is crucial for cilia function and embryonic development. Its absence disrupts Hedgehog signaling, leading to ciliopathies like Joubert syndrome.

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Single-molecule Super-resolution Imaging of Phosphatidylinositol 4,5-bisphosphate in the Plasma Membrane with Novel Fluorescent Probes
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Radiolabeling and Quantification of Cellular Levels of Phosphoinositides by High Performance Liquid Chromatography-coupled Flow Scintillation
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Related Experiment Videos

Last Updated: Mar 9, 2026

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry
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Single-molecule Super-resolution Imaging of Phosphatidylinositol 4,5-bisphosphate in the Plasma Membrane with Novel Fluorescent Probes
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Radiolabeling and Quantification of Cellular Levels of Phosphoinositides by High Performance Liquid Chromatography-coupled Flow Scintillation
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Area of Science:

  • Cell Biology
  • Developmental Biology
  • Genetics

Background:

  • Human ciliopathies, such as Joubert syndrome (JBTS), stem from cilia dysfunction.
  • The inositol polyphosphate 5-phosphatase INPP5E, mutated in JBTS, localizes to cilia, but its precise role is under investigation.
  • Inpp5e knockout mice exhibit JBTS-like phenotypes, including embryonic lethality and developmental defects.

Purpose of the Study:

  • To elucidate the function of INPP5E at cilia and its role in Hedgehog signaling.
  • To investigate the molecular mechanisms underlying Inpp5e deficiency-induced ciliopathy phenotypes.

Main Methods:

  • Utilized mouse genetics to study Inpp5e knockout embryos.
  • Analyzed Hedgehog signaling pathways and cilia function in Inpp5e-deficient cells.
  • Investigated the localization and function of INPP5E using wild-type and mutant forms.

Main Results:

  • Inpp5e knockout embryos displayed aberrant Hedgehog signaling and developmental defects.
  • Increased Hedgehog signaling partially rescued ciliopathy phenotypes in Inpp5e knockout mice.
  • Absence of INPP5E led to phosphoinositide accumulation at the cilia transition zone (TZ), impairing TZ protein recruitment and Smoothened levels.
  • Restoration of INPP5E function normalized TZ organization and Smoothened localization.

Conclusions:

  • INPP5E is essential for maintaining cilia transition zone function and regulating Hedgehog signaling during embryonic development.
  • INPP5E acts as a critical link between phosphoinositide metabolism and Hedgehog signaling at the cilia.
  • Dysfunctional INPP5E contributes to ciliopathies by disrupting cilia signaling pathways.