Skip to content
2000
Volume 21, Issue 10
  • ISSN: 1567-2050
  • E-ISSN: 1875-5828

Abstract

Introduction

Muscarinic 1 acetylcholine receptor (M1AChR) is a member of the G-protein-coupled receptor superfamily, with the dysfunction being linked to the onset of Alzheimer's Disease (AD).

Aims

Retromer complex with Vacuolar Protein Sorting-35 (VPS35) as the core plays an important role in the transport of biological proteins and has been confirmed to be closely related to the pathogenesis of AD. This study was designed to determine whether VPS35 could affect the trafficking mechanism of M1AChRs.

Methods

The interaction between VPS35 and M1AChR was studied by co-immunoprecipitation method, and the recycling of M1AChR influence by VPS35 was analyzed using biotinylation technology.

Results

It was found that VPS35 affected the localization of M1AChR on the cell membrane by regulating intracellular M1AChR transport, thus controlling the M1AChR-mediated cholinergic signaling pathway.

Conclusion

The findings presented here provide a potential pathogenesis and pathway for the treatment of AD.

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/car/10.2174/0115672050356990250111200217
2025-01-28
2025-12-08

  • From This Site

    /content/journals/car/10.2174/0115672050356990250111200217
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. 2016 Alzheimer’s disease facts and figures.Alzheimers Dement.201612445950910.1016/j.jalz.2016.03.00127570871
     [Google Scholar]
  2. EllisJ. DaviesC.H. Understanding G Protein-Coupled Receptors and their Role in the CNSOxford University Press2002349371
     [Google Scholar]
  3. FisherA. PittelZ. HaringR. Bar-NerN. Kliger-SpatzM. NatanN. EgoziI. SonegoH. MarcovitchI. BrandeisR. M1 muscarinic agonists can modulate some of the hallmarks in Alzheimer’s disease: Implications in future therapy.J. Mol. Neurosci.200320334935610.1385/JMN:20:3:34914501019
     [Google Scholar]
  4. FaríasG.G. GodoyJ.A. HernándezF. AvilaJ. FisherA. InestrosaN.C. M1 muscarinic receptor activation protects neurons from β-amyloid toxicity. A role for Wnt signaling pathway.Neurobiol. Dis.200417233734810.1016/j.nbd.2004.07.01615474371
     [Google Scholar]
  5. GenisI. FisherA. MichaelsonD.M. Site-specific dephosphorylation of tau of apolipoprotein E-deficient and control mice by M1 muscarinic agonist treatment.J. Neurochem.199972120621310.1046/j.1471‑4159.1999.0720206.x9886071
     [Google Scholar]
  6. LucasM. GershlickD.C. VidaurrazagaA. RojasA.L. BonifacinoJ.S. HierroA. Structural mechanism for cargo recognition by the retromer complex.Cell2016167616231635.e1410.1016/j.cell.2016.10.05627889239
     [Google Scholar]
  7. Franch-MarroX. WendlerF. GuidatoS. GriffithJ. Baena-LopezA. ItasakiN. MauriceM.M. VincentJ.P. Wingless secretion requires endosome-to-Golgi retrieval of Wntless/Evi/Sprinter by the retromer complex.Nat. Cell Biol.200810217017710.1038/ncb167818193037
     [Google Scholar]
  8. SmallS.A. KentK. PierceA. LeungC. KangM.S. OkadaH. HonigL. VonsattelJ.P. KimT.W. Model-guided microarray implicates the retromer complex in Alzheimer’s disease.Ann. Neurol.200558690991910.1002/ana.2066716315276
     [Google Scholar]
  9. MuhammadA. FloresI. ZhangH. YuR. StaniszewskiA. PlanelE. HermanM. HoL. KreberR. HonigL.S. GanetzkyB. DuffK. ArancioO. SmallS.A. Retromer deficiency observed in Alzheimer’s disease causes hippocampal dysfunction, neurodegeneration, and Aβ accumulation.Proc. Natl. Acad. Sci. USA2008105207327733210.1073/pnas.080254510518480253
     [Google Scholar]
  10. ChenW. NaianX. QilinM. YihongZ. Mechanistic study on the degradation of dopamine receptor D1 by VPS35.J. Apoplexy Nerv. Dis.201936931935
     [Google Scholar]
  11. WangC. NiuM. ZhouZ. ZhengX. ZhangL. TianY. YuX. BuG. XuH. MaQ. ZhangY. VPS35 regulates cell surface recycling and signaling of dopamine receptor D1.Neurobiol. Aging201646223110.1016/j.neurobiolaging.2016.05.01627460146
     [Google Scholar]
  12. IbrahimW.W. IsmailH.M. KhattabM.M. AbdelkaderN.F. Cognitive enhancing effect of diapocynin in D-galactose-ovariectomy-induced Alzheimer’s-like disease in rats: Role of ERK, GSK-3β, and JNK signaling.Toxicol. Appl. Pharmacol.202039811502810.1016/j.taap.2020.11502832360636
     [Google Scholar]
  13. KennedyM.J. DavisonI.G. RobinsonC.G. EhlersM.D. Syntaxin-4 defines a domain for activity-dependent exocytosis in dendritic spines.Cell2010141352453510.1016/j.cell.2010.02.04220434989
     [Google Scholar]
  14. WangC.L. TangF.L. PengY. ShenC.Y. MeiL. XiongW.C. VPS35 regulates developing mouse hippocampal neuronal morphogenesis by promoting retrograde trafficking of BACE1.Biol. Open20121121248125710.1242/bio.2012245123259059
     [Google Scholar]
  15. PerryE. PerryR. BlessedG. TomlinsonB. Necropsy evidence of central cholinergic deficits in senile dementia.Lancet1977309800418910.1016/S0140‑6736(77)91780‑964712
     [Google Scholar]
  16. KellerS.H. LindstromJ. EllismanM. TaylorP. Adjacent basic amino acid residues recognized by the COP I complex and ubiquitination govern endoplasmic reticulum to cell surface trafficking of the nicotinic acetylcholine receptor alpha-Subunit.J. Biol. Chem.200127621183841839110.1074/jbc.M10069120011279119
     [Google Scholar]
  17. YeatmanH.R. LaneJ.R. ChoyK.H.C. LambertN.A. SextonP.M. ChristopoulosA. CanalsM. Allosteric modulation of M1 muscarinic acetylcholine receptor internalization and subcellular trafficking.J. Biol. Chem.201428922158561586610.1074/jbc.M113.53667224753247
     [Google Scholar]
  18. PopovaJ.S. RasenickM.M. Muscarinic receptor activation promotes the membrane association of tubulin for the regulation of Gq-mediated phospholipase Cbeta(1) signaling.J. Neurosci.20002082774278210.1523/JNEUROSCI.20‑08‑02774.200010751428
     [Google Scholar]
  19. HarrisonM.S. HungC.S. LiuT. ChristianoR. WaltherT.C. BurdC.G. A mechanism for retromer endosomal coat complex assembly with cargo.Proc. Natl. Acad. Sci. USA2014111126727210.1073/pnas.131648211124344282
     [Google Scholar]
  20. FisherA. Therapeutic strategies in Alzheimer’s disease: M1 muscarinic agonists.Jpn. J. Pharmacol.200084210111210.1254/jjp.84.10111128032
     [Google Scholar]
/content/journals/car/10.2174/0115672050356990250111200217
Loading
Trafficking of Muscarinic 1 Acetylcholine Receptor Regulated by VPS35 in Alzheimer's Disease
Curr Alzheimer Res 21, 735 (2024); https://doi.org/10.2174/0115672050356990250111200217
/content/journals/car/10.2174/0115672050356990250111200217
/content/journals/car/10.2174/0115672050356990250111200217
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): Alzheimer's disease; muscarinic 1 acetylcholine receptors; retromer complex; trafficking; vacuolar protein sorting-35

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test