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Related Concept Videos

Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

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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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ER Retrieval Pathway01:45

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In the secretory pathway, vesicles transport proteins from one cellular compartment to another in forward transport to deliver the protein to its correct location. Occasionally, misfolded proteins and incorrect proteins escape their original compartments, and a retrieval pathway is used to return the escaped proteins to their original compartment.
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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.
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Recycling Endosomes and Transcytosis00:58

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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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Rab Cascades01:25

Rab Cascades

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Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
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Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
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Investigating Mast Cell Secretory Granules; from Biosynthesis to Exocytosis
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Rab12 Regulates Retrograde Transport of Mast Cell Secretory Granules by Interacting with the RILP-Dynein Complex.

Adi Efergan1, Nurit P Azouz1, Ofir Klein1

  • 1Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel;

Journal of Immunology (Baltimore, Md. : 1950)
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Rab12 regulates mast cell secretory granule transport, controlling retrograde movement via the RILP-dynein complex. This discovery reveals a new mechanism influencing mast cell degranulation and immune responses.

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Area of Science:

  • Cell Biology
  • Immunology
  • Molecular Biology

Background:

  • Secretory granule (SG) transport is essential for regulated exocytosis in activated mast cells.
  • Mast cell degranulation releases inflammatory mediators crucial for immunity and allergic reactions.

Purpose of the Study:

  • To identify novel regulators of mast cell secretory granule transport.
  • To elucidate the mechanism by which these regulators control SG movement and mast cell degranulation.

Main Methods:

  • Stimulus-dependent activation assays for small GTPase Rab12.
  • Microtubule-dependent transport analysis of SGs.
  • Investigation of the RILP-dynein complex in SG retrograde transport.
  • Assessment of Rab12's effect on mast cell degranulation.

Main Results:

  • Rab12 was identified as a novel regulator of mast cell SG transport.
  • Rab12 promotes microtubule-dependent retrograde transport of SGs.
  • The RILP-dynein complex mediates Rab12-dependent minus-end SG transport.
  • Rab12 negatively regulates mast cell degranulation.

Conclusions:

  • Rab12 is a key regulator of mast cell responses.
  • The study reveals the mechanism of retrograde transport for mast cell SGs, involving Rab12 and the RILP-dynein complex.