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Fractionation for Resolution of Soluble and Insoluble Huntingtin Species
Published on: February 27, 2018
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Endosomal recycling defects link Huntington's disease with McLeod syndrome
Elise Marsan1, Eric J Huang1,2
1Department of Pathology, University of California, San Francisco, San Francisco, CA.
The Journal of Cell Biology
|September 16, 2022
Insights
McLeod syndrome protein XK cell surface expression is regulated by endosomal recycling. Mutant huntingtin disrupts this process, reducing manganese transport.
Area of Science:
- Cell Biology
- Neuroscience
- Genetics
Background:
- McLeod syndrome is a rare X-linked condition.
- The XK protein is crucial for red blood cell integrity and manganese transport.
- Dysfunction of XK is implicated in neurological disorders.
Purpose of the Study:
- To investigate the regulation of McLeod syndrome protein XK cell surface expression.
- To determine the impact of mutant huntingtin on XK recycling and function.
Main Methods:
- Utilized cell-based assays to track XK protein localization.
- Employed techniques to study endosomal trafficking pathways.
- Assessed manganese transport in the presence of mutant huntingtin.
Main Results:
- Rab11-mediated endosomal recycling is essential for maintaining XK at the cell surface.
- Mutant huntingtin significantly impairs the recycling of XK.
- Reduced XK cell surface levels correlate with decreased manganese transport.
Conclusions:
- Rab11-dependent endosomal trafficking is a key regulator of McLeod syndrome protein XK.
- Mutant huntingtin disrupts XK recycling, potentially contributing to neurodegeneration through impaired manganese homeostasis.
Abstract:
Chhetri and colleagues (2022. J. Cell Biol.https://doi.org/10.1083/jcb.202112073) show that Rab11-mediated endosomal recycling regulates cell surface expression of McLeod syndrome protein XK. Mutant huntingtin interferes with the recycling of XK to the cell surface and significantly reduces manganese transport across cell membrane.
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