<i>PLEKHG5</i>: Merging phenotypes and disease mechanisms in Charcot‐Marie‐Tooth neuropathy and lower motor neuron disease

Senderek, Jan

doi:10.1111/ene.14752

Euro J of Neurology

2021

DOI: 10.1111/ene.14752

|View full text |Cite

PLEKHG5: Merging phenotypes and disease mechanisms in Charcot‐Marie‐Tooth neuropathy and lower motor neuron disease

Jan Senderek

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2024

Publication Types

Select...

Article1

Relationship

Self Cite0

Independent1

Authors

Journals

Cited by 1 publication

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Plekhg5 controls the unconventional secretion of Sod1 by presynaptic secretory autophagy

Hutchings,

Hambrecht,

Veh

et al. 2024

Nat Commun

View full text Add to dashboard Cite

Increasing evidence suggests an essential function for autophagy in unconventional protein secretion (UPS). However, despite its relevance for the secretion of aggregate-prone proteins, the mechanisms of secretory autophagy in neurons have remained elusive. Here we show that the lower motoneuron disease-associated guanine exchange factor Plekhg5 drives the UPS of Sod1. Mechanistically, Sod1 is sequestered into autophagosomal carriers, which subsequently fuse with secretory lysosomal-related organelles (LROs). Exocytosis of LROs to release Sod1 into the extracellular milieu requires the activation of the small GTPase Rab26 by Plekhg5. Deletion of Plekhg5 in mice leads to the accumulation of Sod1 in LROs at swollen presynaptic sites. A reduced secretion of toxic ALS-linked SOD1G93A following deletion of Plekhg5 in SOD1G93A mice accelerated disease onset while prolonging survival due to an attenuated microglia activation. Using human iPSC-derived motoneurons we show that reduced levels of PLEKHG5 cause an impaired secretion of ALS-linked SOD1. Our findings highlight an unexpected pathophysiological mechanism that converges two motoneuron disease-associated proteins into a common pathway.

show abstract

Plekhg5 controls the unconventional secretion of Sod1 by presynaptic secretory autophagy

Hutchings,

Hambrecht,

Veh

et al. 2024

Nat Commun

View full text Add to dashboard Cite

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

customersupport@researchsolutions.com

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

PLEKHG5: Merging phenotypes and disease mechanisms in Charcot‐Marie‐Tooth neuropathy and lower motor neuron disease

Cited by 1 publication

References 6 publications

Plekhg5 controls the unconventional secretion of Sod1 by presynaptic secretory autophagy

Plekhg5 controls the unconventional secretion of Sod1 by presynaptic secretory autophagy

Contact Info

Product

Resources

About