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Related Concept Videos

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Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
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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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Signal sequences are short amino acid sequences that guide newly synthesized proteins to their proper location within the cell. Classical signal sequences are fifteen to sixty amino acids long and present at the N-terminus of a polypeptide chain. Each signal sequence has a conserved segment of basic residues towards their N terminus, a hydrophobic core, and a C-terminus rich in polar residues. The C-terminus also contains a signal cleavage site and features a -3 -1 sequence motif. The -3-1...
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Imaging pHluorin-tagged Receptor Insertion to the Plasma Membrane in Primary Cultured Mouse Neurons
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ArfGAPs: key regulators for receptor sorting.

Yoko Shiba1, Paul A Randazzo1

  • 1Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD20892, USA.

Receptors & Clinical Investigation
|June 6, 2015
PubMed
Summary
This summary is machine-generated.

ArfGAP proteins are crucial for mammalian cell cargo sorting, ensuring proteins and lipids reach correct organelles. Understanding their mechanisms offers insights into organelle function and potential disease therapies.

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Area of Science:

  • Cell biology
  • Molecular and cell biology
  • Biochemistry

Background:

  • Cellular function relies on precise protein and lipid distribution to organelles.
  • Disruptions in cargo sorting lead to organelle dysfunction and cellular impairment.
  • ArfGAP (ADP-ribosylation factor GTPase-activating protein) family proteins are key regulators of receptor sorting.

Purpose of the Study:

  • To review current knowledge on ArfGAP-mediated cargo sorting mechanisms.
  • To discuss the role of specific ArfGAPs in the sorting of diverse receptors.
  • To explore the therapeutic potential of ArfGAP research in human diseases.

Main Methods:

  • Literature review of studies on ArfGAP function in cargo sorting.
  • Analysis of ArfGAP involvement in vesicle formation and transport.
  • Examination of ArfGAP roles in sorting specific receptors (e.g., MPR, EGFR, TfR, Glut4, TRAIL-R1/DR4, M5-muscarinic receptor, c-KIT, rhodopsin, β1-integrin).

Main Results:

  • ArfGAPs are essential for promoting transport vesicle formation during cargo sorting.
  • Specific ArfGAPs are implicated in the sorting of a wide array of critical cellular receptors.
  • Dysfunctional cargo sorting mediated by ArfGAPs impacts numerous cellular processes.

Conclusions:

  • ArfGAP proteins play a vital role in the fundamental cellular process of cargo sorting.
  • Understanding ArfGAP mechanisms provides mechanistic insight into receptor trafficking.
  • Targeting ArfGAPs may offer novel therapeutic strategies for diseases linked to receptor sorting defects.