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Protein networking: nicotinic acetylcholine receptors and their protein–protein-associations

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Abstract

Nicotinic acetylcholine receptors (nAChR) are complex transmembrane proteins involved in neurotransmission in the nervous system and at the neuromuscular junction. nAChR disorders may lead to severe, potentially fatal pathophysiological states. To date, the receptor has been the focus of basic and applied research to provide novel therapeutic interventions. Since most studies have investigated only the nAChR itself, it is necessary to consider the receptor as part of its protein network to understand or elucidate-specific pathways. On its way through the secretory pathway, the receptor interacts with several chaperones and proteins. This review takes a closer look at these molecular interactions and focuses especially on endoplasmic reticulum biogenesis, secretory pathway sorting, Golgi maturation, plasma membrane presentation, retrograde internalization, and recycling. Additional knowledge regarding the nAChR protein network may lead to a more detailed comprehension of the fundamental pathomechanisms of diseases or may lead to the discovery of novel therapeutic drug targets.

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Abbreviations

APC:

Adenomatous polyposis coli

BiP:

Binding immunoglobulin protein

COG:

Conserved oligomeric Golgi

COP:

Coat protein complex

DGC:

Dystrophin-associated glycoprotein complex

ER:

Endoplasmic reticulum

ERAD:

ER-associated degradation

ERES:

ER entry site

ERGIC:

ER-Golgi intermediate compartment

GlcNAc:

N-acetylglucosamine

GRASP:

Golgi reassembly stacking protein

MAPK:

Mitogen-activated protein kinase

MASC:

Muscle accessory-specific component

MuSK:

Muscle-specific kinase

MVB:

Multivesicular body

nAChR:

Nicotinic acetylcholine receptors

rapsyn:

Receptor-associated protein at synapse

RATL:

Rapsyn-associated transmembrane linker

RER1:

Receptor for ER 1

TANGO:

Transport and Golgi organization

TGN:

Trans-Golgi network

UGGT1:

UDP-glucose: glycoprotein glucosyltransferase-1

VVA B4 :

Vicia villosa agglutinin B4

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Acknowledgements

We would like to thank Prof. Dr. Horst Thiermann for assigning the topic of the nicotinic acetylcholine receptor and for his extensive support.

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  1. Bundeswehr Institute of Pharmacology and Toxicology, Munich, Bavaria, Germany

    Sabrina Brockmöller, Franz Worek & Simone Rothmiller

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All authors contributed to the manuscript conception and design. Review collection and formal conceptualization were performed by Sabrina Brockmöller. The first draft of the manuscript was written by Sabrina Brockmöller and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Brockmöller, S., Worek, F. & Rothmiller, S. Protein networking: nicotinic acetylcholine receptors and their protein–protein-associations. Mol Cell Biochem (2024). https://doi.org/10.1007/s11010-024-05032-x

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