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Related Concept Videos

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.
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
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Protein Translocation Machinery on the ER Membrane01:28

Protein Translocation Machinery on the ER Membrane

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The translocon complex situated on the ER membrane is the main gateway for the protein secretory pathway. It facilitates the transport of nascent peptides into the ER lumen and their insertion into the ER membrane.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the...
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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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Cotranslational Protein Translocation01:20

Cotranslational Protein Translocation

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Translocation of proteins across membranes is an ancient process that occurs even in bacteria and archaebacteria. In fact, the components of the translocation machinery are still conserved between prokaryotes and eukaryotes.
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
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Tail-anchoring of Proteins in the ER Membrane01:45

Tail-anchoring of Proteins in the ER Membrane

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Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...
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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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Related Experiment Video

Updated: Mar 22, 2026

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species
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Fractionation for Resolution of Soluble and Insoluble Huntingtin Species

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Membrane-associated Rhes-Slc4a7 complex orchestrates tunneling nanotube formation and mutant Huntingtin spread.

Sunayana Dagar1,2,3, Alexandra Fernandez4, Uri Nimrod Ramírez-Jarquín5

  • 1Department of Chemistry/Biochemistry, Florida Atlantic University, Boca Raton, FL 33431, USA.

Science Advances
|March 20, 2026
PubMed
Summary

Researchers discovered that Slc4a7 is crucial for tunneling nanotubes (TNTs) to transfer mutant Huntingtin (mHTT) in Huntington disease (HD). Inhibiting Slc4a7 reduces mHTT spread, offering a potential therapeutic target for HD.

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Detection and Quantification of Tunneling Nanotubes Using 3D Volume View Images
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Detection and Quantification of Tunneling Nanotubes Using 3D Volume View Images

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Generation of Native, Untagged Huntingtin Exon1 Monomer and Fibrils Using a SUMO Fusion Strategy
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Generation of Native, Untagged Huntingtin Exon1 Monomer and Fibrils Using a SUMO Fusion Strategy

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Related Experiment Videos

Last Updated: Mar 22, 2026

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species
07:08

Fractionation for Resolution of Soluble and Insoluble Huntingtin Species

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Detection and Quantification of Tunneling Nanotubes Using 3D Volume View Images
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Detection and Quantification of Tunneling Nanotubes Using 3D Volume View Images

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Generation of Native, Untagged Huntingtin Exon1 Monomer and Fibrils Using a SUMO Fusion Strategy
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Generation of Native, Untagged Huntingtin Exon1 Monomer and Fibrils Using a SUMO Fusion Strategy

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Tunneling nanotubes (TNTs) facilitate intercellular protein transfer, including mutant Huntingtin (mHTT), implicated in Huntington disease (HD).
  • The ras homolog enriched in the striatum (Rhes) protein regulates TNT formation and mHTT transmission, but its molecular partners were unknown.

Purpose of the Study:

  • To identify molecular components involved in Rhes-mediated TNT formation and mHTT intercellular transfer.
  • To elucidate the mechanism by which Rhes regulates TNTs and mHTT transmission.

Main Methods:

  • Unbiased liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify Rhes-interacting proteins.
  • Functional studies using small interfering RNA (siRNA) and pharmacological inhibitors of Slc4a7.
  • Analysis of Rhes-Slc4a7 interaction domains and Rhes farnesylation.
  • In vivo studies using Slc4a7 knock-out mice.

Main Results:

  • Slc4a7 (solute carrier family 4 member 7), an intracellular pH sensor, was identified as a key membrane-binding partner of Rhes.
  • Slc4a7 depletion or inhibition significantly reduced Rhes-induced TNT formation and mHTT intercellular transfer.
  • Rhes directly interacts with Slc4a7, modulating intracellular pH to promote TNT formation, independent of Slc4a7's transporter activity.
  • Inhibition of Rhes farnesylation disrupted Rhes-Slc4a7 binding and abolished TNT formation.
  • Slc4a7 knock-out mice exhibited reduced in vivo striatal mHTT transmission.

Conclusions:

  • A novel Rhes-Slc4a7 signaling axis is critical for TNT-mediated mHTT transmission in Huntington disease.
  • Slc4a7 plays a pivotal role in regulating TNT formation and mHTT spread.
  • Slc4a7 represents a potential therapeutic target for limiting disease progression in Huntington disease.