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Related Concept Videos

Lysosomal Hydrolases01:22

Lysosomal Hydrolases

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,...
Lysosomes01:31

Lysosomes

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,...
Lysosomes01:31

Lysosomes

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,...
Overview of Protein Sorting and Transport01:45

Overview of Protein Sorting and Transport

Eukaryotic cells have different membrane-bound organelles with distinct protein requirements. The process by which proteins are targeted to a specific organelle is called protein sorting.
Protein sorting can be of two types: signal-based sorting and vesicle-based trafficking. In signal-based sorting, specific amino acid sequences called sorting signals target proteins to the proper location inside the cell either via gated transport or by protein translocation.  In gated transport, folded...
Mitochondrial Protein Sorting01:39

Mitochondrial Protein Sorting

Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death.  Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...

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Characterization of Neuronal Lysosome Interactome with Proximity Labeling Proteomics
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Published on: June 23, 2022

Sorting of lysosomal proteins.

Thomas Braulke1, Juan S Bonifacino

  • 1University Medical Center Hamburg-Eppendorf, Department Biochemistry, Children's Hospital Research campus, Martinistr.52, 20246, Hamburg, Germany. braulke@uke.uni-hamburg.de

Biochimica Et Biophysica Acta
|December 3, 2008
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Lysosomes utilize distinct protein pathways, including mannose 6-phosphate (M6P) tagging and M6P-independent routes, to ensure correct protein delivery. Sorting signals and receptor interactions guide these essential lysosomal transport mechanisms.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Lysosomes are vital organelles requiring precise protein targeting for function.
  • Soluble and transmembrane proteins are directed to lysosomes via signal-dependent mechanisms.

Purpose of the Study:

  • To elucidate the diverse mechanisms governing protein transport to lysosomes.
  • To detail the roles of mannose 6-phosphate (M6P) and M6P-independent pathways.
  • To explore the function of sorting signals and their interactions in protein trafficking.

Main Methods:

  • Analysis of protein modification (e.g., M6P tagging).
  • Identification of lysosomal receptors (e.g., M6P receptors, LIMP-2, sortilin).
  • Characterization of cytosolic sorting signals (dileucine-based, tyrosine-based motifs).
  • Investigation of regulatory factors like phosphorylation and lipid modifications.

Main Results:

  • The mannose 6-phosphate (M6P) pathway is crucial for most soluble acid hydrolases.
  • Alternative M6P-independent pathways involve receptors like LIMP-2 and sortilin for other proteins.
  • Cytosolic sorting signals, including dileucine and tyrosine motifs, mediate cargo receptor and transmembrane protein sorting.
  • Phosphorylation and lipid modifications fine-tune lysosomal protein trafficking.

Conclusions:

  • Lysosomal protein targeting is a complex process involving multiple coordinated pathways.
  • Both luminal and cytosolic signals, along with specific receptors, ensure accurate protein delivery to lysosomes.
  • Understanding these mechanisms is key to comprehending lysosome biogenesis and function.