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Lysosomes01:31

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Lysosomes are membrane-enclosed spherical sacs derived from the Golgi apparatus. The most important function of the lysosome is degrading macromolecules and biological polymers that are released during membrane trafficking events such as the secretory, endocytic, autophagic, and phagocytic pathways. The degradation is carried out by several hydrolytic enzymes active in an acidic environment of the lysosomal lumen. These acid hydrolases are involved in cellular processes such as cell signaling,...
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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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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.
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In eukaryotic cells,  cytoskeletal filaments such as actin, microtubules, and intermediate filaments form a mesh-like cytoskeletal network. These filaments serve as tracks for transporting cellular cargo. Specialized motor proteins use the chemical energy stored in adenosine triphosphate (ATP) for this transport. During interphase, microtubules are polarized, with the plus-end towards the cell periphery and the minus-end towards the cell center. Two microtubule-associated motor proteins,...
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PKA orchestrates long-range lysosomal vesicle transport during synaptic maintenance.

Kerriann K Badal1,2, Yibo Zhao1, Bindu L Raveendra1

  • 1Department of Neuroscience, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, 130 Scripps Way, Jupiter, FL 33458, USA.

Iscience
|December 16, 2025
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Summary

Synapse maintenance involves decreased retrograde lysosomal vesicle transport, while formation boosts anterograde mitochondrial transport. Protein Kinase A (PKA) regulates this organelle transport during synaptic plasticity.

Keywords:
cell biologymolecular biologyneuroscience

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Bidirectional long-distance organelle transport is vital for neuronal communication.
  • Regulation of organelle transport during synapse development and plasticity is not well understood.

Purpose of the Study:

  • To investigate the regulation of organelle transport during synapse formation, maintenance, and plasticity in the Aplysia sensory neuron-motor neuron system.
  • To identify key molecular players involved in regulating this transport.

Main Methods:

  • Utilized the Aplysia gill-siphon withdrawal reflex model.
  • Monitored organelle transport (lysosomal vesicles and mitochondria) using microscopy.
  • Conducted pharmacological screening to identify regulatory molecules.

Main Results:

  • Synapse maintenance correlated with reduced retrograde lysosomal vesicle (LV) transport.
  • Anterograde mitochondrial transport increased within 12 hours of synapse formation.
  • Serotonin-induced synapse formation suppressed retrograde LV transport and enhanced anterograde mitochondrial transport.
  • Protein Kinase A (PKA) was identified as a key regulator of retrograde LV transport.

Conclusions:

  • Organelle transport is differentially regulated during distinct phases of synaptic development and plasticity.
  • Retrograde LV transport and anterograde mitochondrial transport exhibit distinct temporal dynamics.
  • PKA plays a crucial role in modulating organelle transport for synapse maintenance.