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Related Concept Videos

Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

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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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The Early Endosome: Endocytosis of Transferrin01:28

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Essential proteins such as insulin or low-density lipoprotein (LDL) and micronutrients such as iron enter a eukaryotic cell through receptor-mediated endocytosis. Subsequently, the early endosomes fuse with the vesicles containing such receptor-ligand complexes and play a vital role in sorting the incoming ligands and receptors. While the ligands are either degraded inside the vesicle or released into the cytosol, their receptors are returned to the plasma membrane for further rounds of...
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Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
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Maturation of Endosomes01:28

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The early endosome containing internalized molecules matures through transformations in its location, morphology, intraluminal pH, and membrane protein composition. Together, these changes result in a more acidic late endosome that contains multiple intraluminal vesicles; therefore, the late endosome is also called a multivesicular body (MVB).
Changes in location
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Overview of Secretory Vesicles01:33

Overview of Secretory Vesicles

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Secretory vesicles, also known as dense core vesicles (DCVs), are membrane-bound vesicles that transport secretory proteins, such as hormones or neurotransmitters. Regulated secretory vesicles transport proteins from the trans-Golgi network to the exterior of the cell. Proteins present in regulated secretory vesicles are required to be rapidly exocytosed in large amounts upon a specific stimulus.
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
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SNAREs and Membrane Fusion01:43

SNAREs and Membrane Fusion

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Once a transport vesicle has recognized its target organelle, the vesicular membrane needs to fuse with the target membrane to unload the cargo. Transmembrane proteins called SNAREs present on organelle membranes and their vesicles, mediate vesicle fusion.
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Updated: Nov 14, 2025

Differential Labeling of Cell-surface and Internalized Proteins after Antibody Feeding of Live Cultured Neurons
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ALS2 regulates endosomal trafficking, postsynaptic development, and neuronal survival.

Joohyung Kim1,2, Sungdae Kim2, Minyeop Nahm2

  • 1Department of Brain and Cognitive Sciences, Seoul National University, Seoul, Korea.

The Journal of Cell Biology
|March 8, 2021
PubMed
Summary

The ALS2 gene

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Area of Science:

  • Neuroscience
  • Genetics
  • Cell Biology

Background:

  • Mutations in the human ALS2 gene are linked to juvenile amyotrophic lateral sclerosis.
  • The physiological functions of the ALS2 protein, a guanine-nucleotide exchange factor for Rab5, are not well understood.

Purpose of the Study:

  • To investigate the roles of the Drosophila homologue of ALS2 (dALS2) in neuronal development and function.
  • To elucidate the molecular mechanisms underlying dALS2's function in the nervous system.

Main Methods:

  • Utilized Drosophila melanogaster as a model organism.
  • Investigated dALS2 function in postsynaptic development and endosomal trafficking.
  • Examined age-dependent neurodegenerative phenotypes.

Main Results:

  • dALS2 promotes postsynaptic development by activating the Frizzled nuclear import (FNI) pathway.
  • dALS2 loss leads to defects in subsynaptic reticulum structure and endosome trafficking.
  • dALS2 loss results in age-dependent locomotor impairment and neurodegeneration, independent of the FNI pathway.

Conclusions:

  • dALS2 plays critical roles in synaptic development and neuronal survival.
  • dALS2 regulates endosomal trafficking and FNI pathway activation.
  • dALS2 dysfunction contributes to age-dependent neurodegenerative phenotypes resembling ALS.