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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.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
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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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Amplifying Signals via Enzymatic Cascade01:22

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When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
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What are Second Messengers?01:12

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Because many receptor binding ligands are hydrophilic, they do not cross the cell membrane and thus their message must be relayed to a second messenger on the inside. There are several second messenger pathways, each with their own way of relaying information. G-protein coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol path is active when the receptor induces phospholipase C to hydrolyze the phospholipid,...
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Amplifying Signals via Second Messengers01:15

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Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
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GPI Anchoring of Proteins in the ER Membrane01:29

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GPI-anchoring is a post-translational, reversible protein modification that is ubiquitous in eukaryotes. Such proteins are primarily present on the exoplasmic leaflet of the plasma membrane.
GPI-anchor structure
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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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Un mecanismo de conversión de fosfoinosítidos para la salida de los endosomas

Katharina Ketel1, Michael Krauss1, Anne-Sophie Nicot2

  • 1Leibniz-Institut für Molekulare Pharmakologie, 13125 Berlin, Germany.

Nature
|January 14, 2016
PubMed
Resumen

La identidad de la membrana celular se basa en los fosfoinosítidos. Este estudio revela que MTM1 convierte el fosfatidilinositol 3-fosfato (PI(3) en fosfatidilinositol 4-fosfato (PI(4) para la exocitosis, vinculando los defectos a la miopatía miotubular.

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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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Área de la Ciencia:

  • Biología celular
  • Biología molecular
  • La bioquímica

Sus antecedentes:

  • Los fosfoinosítidos regulan las funciones vitales de las células, incluida la señalización y el tráfico de membranas.
  • Los fosfoinosítidos específicos marcan los compartimentos celulares; el fosfatidilinositol 3-fosfato (PI(3) P) se encuentra en los endosomas, mientras que el fosfatidilinositol 4-fosfato (PI(4) P) se encuentra en la membrana plasmática.
  • La conversión regulada de los fosfoinosítidos es esencial para el tráfico direccional de la membrana entre las vías endosómicas y secretoras.

Objetivo del estudio:

  • Elucidar el mecanismo molecular de la conversión de fosfoinosítidos durante la salida de carga endosómica a través de la exocitosis.
  • Investigar el papel de la fosfatidilinositol 3-fosfatasa MTM1 en este proceso.
  • Para explorar el vínculo entre la conversión defectuosa de fosfoinosítidos y la miopatía centronuclear ligada al X.

Principales métodos:

  • Investigó el papel de MTM1 en la entrega de carga desde los endosomas a la superficie celular.
  • Se ha analizado la dinámica de los fosfoinosítidos mediante ensayos bioquímicos.
  • Examinó el reclutamiento del complejo de exocisto a los endosomas.

Principales resultados:

  • La entrega de carga endosómica a la superficie requiere la hidrólisis de PI(3) P por MTM1.
  • La eliminación dependiente de MTM1 de PI(3) P se combina con la generación mediada por PI4K2α de PI(4) P.
  • Este interruptor fosfoinosítido facilita el reclutamiento del complejo de exocistos y la fusión de la membrana para la exocitosis.

Conclusiones:

  • Se ha establecido un mecanismo para la conversión de los fosfoinosítidos de PI(3) P a PI(4) P en los endosomas durante la exocitosis.
  • La función defectuosa de MTM1 altera esta conversión, lo que lleva a una exocitosis deteriorada.
  • Este defecto de conversión de fosfoinosítidos se propone como la causa subyacente de la miopatía centronuclear ligada al X.