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Delivery Pathways to the Lysosome01:36

Delivery Pathways to the Lysosome

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Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
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Autophagy01:27

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Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
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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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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).
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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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The recycling endosome, also known as the endosomal recycling compartment (ERC), is a part of the slow-recycling process of the endocytic pathway. Molecules internalized through receptor-mediated endocytosis are either degraded in the lysosomes or are recycled to the plasma membrane through the fast- or slow-recycling route.
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Measuring Synaptic Vesicle Endocytosis in Cultured Hippocampal Neurons
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Autophagy and the endolysosomal system in presynaptic function.

Maria Andres-Alonso1,2, Michael R Kreutz3,4,5,6, Anna Karpova7,8

  • 1Research Group Neuroplasticity, Leibniz Institute for Neurobiology, 39118, Magdeburg, Germany.

Cellular and Molecular Life Sciences : CMLS
|December 19, 2020
PubMed
Summary

Neurons maintain protein balance (proteostasis) through autophagy and the endolysomal system. These pathways are crucial for presynaptic function, clearing damaged proteins and supporting synaptic signaling.

Keywords:
AutophagyAxonal boutonsEndolysosomal systemProteostasisSynaptic plasticity

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Area of Science:

  • Neuroscience
  • Cell Biology

Background:

  • Neuronal proteostasis faces challenges due to the distance between protein synthesis/degradation sites (soma) and synaptic junctions.
  • Presynaptic sites have high protein turnover demands from vesicle cycling, requiring efficient protein delivery and removal.

Purpose of the Study:

  • To review the roles of autophagy and the endolysomal system in presynaptic protein turnover.
  • To discuss the regulation, cargo, and interplay of these pathways in neurons.
  • To explore emerging non-canonical functions in synaptic plasticity.

Main Methods:

  • Literature review synthesizing evidence on autophagy and endolysomal pathways in presynaptic function.
  • Analysis of molecular mechanisms governing cargo collection, transport, and degradation.
  • Discussion of recent findings on degradative organelles in synaptic signaling.

Main Results:

  • Both autophagy and the endolysomal system are critical for clearing damaged proteins at presynaptic terminals.
  • These pathways are regulated by presynaptic machinery and handle specific protein cargoes.
  • Evidence suggests non-canonical roles in synaptic signaling and plasticity.

Conclusions:

  • Autophagy and the endolysomal system are essential for maintaining presynaptic proteostasis and function.
  • Their interplay is vital for neuronal health and synaptic plasticity.
  • Further research into their non-canonical roles could reveal new therapeutic targets.